The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Bone scintigraphy in chondroblastoma

Scintigraphy in 3 patients with chondroblastoma showed that the tumors were hyperemic and avidly accumulated the radionuclide. These changes were also present in adjacent normal bone, but to a lesser degree. This suggest that radionuclide uptake in chondroblastoma is a function of the blood supply to the tumor rather than primary matrix extraction.     

Congenital hepatic artery aneurysm simulating pancreatic carcinoma

The authors report a case of a hepatic artery aneurysm that simulated a mass in the head of the pancreas. The correct diagnosis was made preoperatively based on several findings: curvilinear calcification within the mass on CT, a well-defined cystic collection on ultrasound, absence of biliary duct dilatation or jaundice, and presence of other aneurysms.     

The protein product of the proto-oncogene c-cbl forms a complex with phosphatidylinositol 3-kinase p85 and CD19 in anti-IgM-stimulated human B-lymphoma cells

Multiple signal transduction cascades, consisting of multiple interacting proteins, are activated following stimulation through most cell surface receptors, including the immunoglobulin receptor of B lymphocytes. In this report, we investigated the multimolecular complexes formed following anti-Ig stimulation of a human B-lymphoma cell line, resulting in activation of phosphatidylinositol 3-kinase (PI3K). PI3K is a lipid kinase that consists of an 85-kD regulatory subunit, bound to a 110-kD catalytic subunit. CD19 is a 95-kD B-cell surface marker that contains a consensus binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K activity in activated B cells. The protein product of the c-cbl protooncogene is a 120-kD protein that is expressed in early B-lineage cells and in myeloid cells and is phosphorylated on tyrosine following receptor-mediated signaling in T and B lymphocytes. We demonstrate here that phosphorylated c-cbl complexes with CD19 and with PI3Kp85 via its C-terminal SH2 domain, and that both c-cbl and CD19 are associated with active PI3K in anti-Ig- stimulated cells. Although we cannot differentiate between a three- component, c-cbl/CD19/p85 complex and individual two-component complexes, these studies suggest that c-cbl may function as a docking protein, possibly linking distinct signal transduction pathways.     

Active immunization of murine allogeneic bone marrow transplant donors with B-cell tumor-derived idiotype: a strategy for enhancing the specific antitumor effect of marrow grafts

Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with allogeneic bone marrow transplantation (BMT) for lymphomas and multiple myeloma. We used the C3H 38C13 murine B-cell lymphoma, which expresses and secretes clonally derived Ig, the idiotype of which can serve as a tumor-specific antigen, to test the principle of transfer of tumor idiotype-specific immunity with BM. BALB/c marrow donors were twice immunized with 38C13-derived Ig, or with an isotype-matched control Ig, conjugated to keyhole limpet hemocyanin. Lethally irradiated C3H recipients reconstituted with marrow from idiotype immune, but not nonspecifically immune, donors demonstrated protection against subsequent lethal tumor challenge. The immunoprotective effect of immune allogeneic marrow was abrogated by T-cell depletion of the marrow graft before infusion. Low levels of serum anti-idiotypic antibody remained unaltered in recipients of T-cell-depleted immune marrow, consistent with a primary role for T-cell immunity in the cellular mechanism of this phenomenon. A modest therapeutic effect of immune allogeneic marrow was observed against 10 day, 1 cm established subcutaneous tumors, but only in combination with a booster immunization of the recipient post-BMT. These results provide the rationale for a novel strategy for enhancing the specific antitumor effect of allogeneic marrow grafts.     

Blood transfusion exposure does not influence survival in patients with carcinoma of the breast

There is abundant evidence of immune modulation induced by exposure to blood transfusions. Some studies have demonstrated a detrimental effect of transfusion on the recurrence of malignant disease and survival. We retrospectively studied the impact of blood transfusion exposure on 229 patients with breast cancer who were seen from July 1973 to September 1980, had at least 5 years' follow-up and had been randomized by therapy at the time of diagnosis. The patients were divided into four groups according to transfusion history: Group 1 (111 patients), no transfusion; Group 2 (34 patients), first transfusion after mastectomy; Group 3 (41 patients), first transfusion at mastectomy; and Group 4 (43 patients), first transfusion before mastectomy. All transfused patients received red cells or whole blood or both. At the time of analysis, 124 (54%) of the patients had died. Only Group 2 was statistically associated with decreased survival; recurrence of disease was 85 percent in this group, compared with 53 percent to 61 percent in the other three groups (p = 0.006, log-rank test). In general, Group 2 patients received transfusions because of recurrent disease. We conclude that transfusions before or at mastectomy are not associated with increased recurrence or reduced survival in patients with breast cancer.