Intracellular fate of endocytosed collagen in rat liver endothelial cells.

The fate of endocytosed collagen (COL) in sinusoidal liver endothelial cells was studied using COL labeled with FITC (F-COL) or iodine (125I-COL) or both (125I-FCOL). In pulse-chase experiments in vitro, F-COL localized after 10 min along the limiting membrane of vesicles, taking the appearance of rings. After 20 min chase the probe appeared more concentrated in fewer but larger ring structures, and after 60 min the probe was observed mainly in the interior of smaller vesicles. Gel filtration of solubilized cultures after pulse-chase experiments using 125I-FCOL or 125I-COL revealed that degradation was initiated and largely completed in the small, filled vesicles, judged as a pre- or early lysosomal compartment. In the presence of monensin, or by incubation at 20 degrees C, the probe was arrested at the level of the larger ring structures, and degradation could not be observed. Lysosomal preloading by iv injection of TRITC-COL (T-COL) 24 h prior to pulse-chase experiments with culture cells using F-COL disclosed colocalization of the two dyes only after 8 h in perinuclear vesicles of a size larger than the early lysosomal vesicles observed after 60 min, suggesting a slow, unidirectional transport of F-COL to the T-COL labeled lysosomal compartment. Esterase reaction product was observed mainly in vesicles resembling the double-stained lysosomes. We conclude that (1) the early endosomes, (2) the vesicles appearing after 60 min are prelysosomes mediating degradation, and (3) the lysosomes accumulating in the probe after 8 h are responsible for final degradation and storage of residual stain.

Multiple myeloma in central and northern Norway 1981-1982: a follow-up study of a randomized clinical trial of 5-drug combination therapy versus standard therapy.

In a randomized study of 92 previously untreated patients with multiple myeloma, the intention was to document the possible beneficial effect of combination chemotherapy including vincristine, carmustine, alkylating agents and prednisone, as compared to conventional therapy with melphalan and prednisone. Major prognostic factors did not differ significantly between the treatment groups. With the 2-drug therapy and 5-drug combination therapy, 48 and 54% of the patients achieved remission, respectively. Median survival for patients treated with the 2-drug regimen and 5-drug regimen was 29 and 33.5 months, respectively. No significant difference was found between the survival curves for stage III patients treated with the two regimens. After 12 months, patients who had achieved remission were randomized to have treatment discontinued or to have maintenance treatment. The numbers of relapses, remission duration and survival of the two groups were similar.

Multiple myeloma in central Norway 1981-1982: a randomized clinical trial of 5-drug combination therapy versus standard therapy.

67 previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of combination chemotherapy including vincristine, carmustine, alkylating agents, and prednisone was more effective than conventional therapy with melphalan and prednisone. The treatment groups did not show significant differences with respect to major prognostic factors. With the 2-drug combination therapy and 5-drug combination therapy, 67 and 74% of the patients achieved remission, respectively. Moreover, no significant difference was found between the two treatment schedules in terms of median survival (30+ months). The survival curves for stage III patients treated with the two regimens did not differ significantly. After 12 months, patients who had achieved remission were randomized to have treatment discontinued or to have maintenance treatment. 7 of 15 patients on maintenance therapy relapsed, whereas 9 of 14 patients who had their therapy discontinued relapsed, and the survival of the two groups was similar.