Tyrosine phosphorylation of the alpha and beta subunits of the type I interferon receptor. Interferon-beta selectively induces tyrosine phosphorylation of an alpha subunit-associated protein

We studied the phosphorylation of the alpha and beta subunits of the Type I interferon (IFN) receptor induced by Type I IFNs in the human U-266 and MOLT-4 cell lines. Both IFN-alpha and IFN-beta induced tyrosine phosphorylation of the beta subunit of the receptor. The Type I IFN-induced tyrosine phosphorylation of the beta subunit was rapid and transient, being detectable within 1 min of Type I IFN treatment and gradually diminishing to almost base-line levels by 60 min. All Type I IFNs studied were found to induce tyrosine phosphorylation of the alpha subunit of the Type I IFN receptor, the p135tyk2 and JAK-1 tyrosine kinases, and the ISGF3 alpha components. Interestingly, IFN-beta, but not IFN-alpha or IFN-omega, induced tyrosine phosphorylation of an alpha subunit-associated protein with an apparent molecular mass of approximately 100 kDa (p100). These data suggest the existence of a common signaling pathway(s) for Type I IFNs involving the alpha and beta subunits of the receptor, the tyrosine kinases p135tyk2 and JAK-1, and the ISGF3 alpha components. However, differences between the signaling pathways of different Type I IFNs exist, as suggested by tyrosine phosphorylation of an alpha subunit-associated protein only in response to IFN-beta.     

Portal hypertension in schistosomiasis: a long-term follow-up of a randomized trial comparing three types of surgery

The long-term follow-up of patients with the severe form of Manson's schistosomiasis who had had elective surgical treatment for portal hypertension, in a randomized trial, was clinically evaluated. Of 94 patients, proximal splenorenal shunting was performed in 32, esophagogastric devascularization with splenectomy in 32 and distal splenorenal shunting in 30. Patients were observed during a mean of 85.7 +/- 33.1 mo, excluding nine patients (9.6%) who were lost to follow-up. Recurrence of upper gastrointestinal tract bleeding occurred in 24.1% of the patients, without statistical differences among the three groups, but rebleeding because of varices was more frequent after esophagogastric devascularization with splenectomy. Hepatic encephalopathy was significantly higher after proximal splenorenal shunting (39.3%) when compared with distal splenorenal shunting (14.8%) and with esophagogastric devascularization with splenectomy (0%). Lethality was also significantly higher after proximal splenorenal shunting (42.9%) when compared with distal splenorenal shunting (14.8%) and with esophagogastric devascularization with splenectomy (7.1%). Indirect hyperbilirubinemia was absent after esophagogastric devascularization with splenectomy and more frequent after distal splenorenal shunting (52%) although also present after proximal splenorenal shunting (29.6%). Esophagogastric devascularization with splenectomy was demonstrated to be the best option because of the absence of encephalopathy and because of low mortality rates. Hepatic encephalopathy occurred after distal splenorenal shunting but in a lesser percentage than after proximal splenorenal shunting. The higher incidence of encephalopathy and lethality proscribes proximal splenorenal shunting in Manson'schistosomiasis.     

Regulation of pituitary beta-endorphin secretion in aging rats: in vitro responsiveness to dopamine

The intermediate lobe of the mammalian pituitary is highly responsive to dopamine inhibition of beta-endorphin secretion. In this study, the ability of aged (12 months) intermediate lobes to respond to dopamine was compared to that of young (6 weeks) tissue, using a short-term in vitro incubation of isolated rat neurointermediate lobes, with measurement of peptide release by radioimmunoassay. Tissue from the aged rats released greater amounts of beta-endorphin peptide than amounts measured from young tissue at all time periods studied. The aged lobes were also found to be significantly more sensitive to dopamine than young glands, as measured by percent change of each group compared to respective baseline release. In comparison, incubation of tissue from young animals in which the intermediate lobe had been acutely denervated by treating rats with injections of the catecholamine neurotoxin, 6-hydroxydopamine, did not differ in responsiveness to dopamine as compared to tissue from control rats. The observations suggest that aging intermediate lobe, while being hypersecretory, is supersensitive to dopamine, perhaps as the result of gradually reduced innervation.     

I-123 MIBG scintigraphy in adults. A report of clinical experience

Thirty-one adult patients with clinical findings suggestive of pheochromocytoma were studied with I-123 MIBG. All patients had images obtained at 24 and 48 hours. Five patients had abnormal uptake proved to be because of I-123 MIBG avid tumors. The remaining 26 patients had no proven tumors and showed physiologic uptake in various organs. The 24-hour images were of high quality. In all cases, the 48-hour images contributed no significant additional information. Only in 1 patient did the 48-hour image add some certainty. Physiologic uptake was seen in the salivary glands, liver, G.I. tract, and urinary bladder in all patients (100%). Uptake was also observed in the lung and heart (90%), normal adrenal glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%). The authors' experience indicates that I-123 MIBG gives superior images compared to the previously used I-131 MIBG, that the optimum imaging time for adults is 18-24 hours, and that normal distribution patterns including uterine and neck muscle uptake should be familiar to physicians interpreting the studies.