Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.     

REM sleep behavior disorder and vocal cord paralysis in Machado-Joseph disease.

We evaluated the occurrence of REM sleep behaviour disorder (RBD) and vocal cord abductor paralysis (VCAP) in a group of 9 Machado-Joseph disease (MJD) patients. RBD was diagnosed by clinical history plus audiovisual polysomnography in 4 men and 1 woman (55%). While dreaming, 4 fell out of the bed and the other injured his arms. Laryngoscopy detected bilateral VCAP in 1 patient with stridor who required emergency tracheotomy, and partial vocal cord abductor restriction in 2. RBD and VCAP are two potentially injurious conditions that should be considered part of the clinical spectrum of MJD.     

Outcome of hospitalized patients with COVID-19 pneumonia treated with high-dose immunoglobulin therapy in a prospective case series

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Studies concerning the structure and organization of the vaccinia virus nucleoid. I. Isolation and characterization of subviral particles prepared by treating virions with guanidine-HCL, nonidet-P40, and 2-mercaptoethanol

Subviral particles (Gu-subviral particles) containing DNA complexed with 20–25% of the protein found in complete virus particles could be isolated after treating purified vaccinia virions with 8 M guanidine-HCI, 1% Nonidet-P40, and 1% 2-mercaptoethanol. Electron microscopic examination of the Gu-subviral particles fixed with glutaraldehyde and formaldehyde, revealed spherical structures, 300–350 nm in diameter. DNA in combination with protein was observed to be further folded into globular structures, 200–600 Å in diameter on the surface of the particles. Analysis of the proteins in Gu-subviral particles by SDS-polyacrylamide gel electrophoresis showed that 10 polypeptides with molecular weights of 120K, 90K, 68K, 61K, 58K, 32K, 27K, 24K, 14.5K, and 10K were associated with the viral DNA. After dialysis, the particles could be shown to have retained, in part, the capacity to catalyze the synthesis of RNA in vitro.