Phenobarbital promotes the development of adenocarcinomas in the accessory sex glands of MNU-inoculated L-W rats.

Aged Lobund-Wistar (L-W) rats develop: (i) spontaneous and induced metastasizing adenocarcinomas in the prostate and seminal vesicle (P-SV) complex; and (ii) spontaneous hepatomas and hepatocarcinomas. Within the time-frame of 14 months, similar adenocarcinomas were induced in the P-SV complex in 70-90% of younger L-W rats by a single i.v. inoculation of methylnitrosourea (MNU) which was followed by slow release s.c. implants of testosterone propionate (TP). Within the same time-frame, neither MNU nor TP alone induced significant incidences of P-SV tumors; and untreated control L-W rats were disease-free. Methylnitrosourea or TP and combinations thereof did not induce liver tumors. However, when MNU-inoculated L-W rats were fed phenobarbital (PB), they developed (i) metastasizing adenocarcinomas in the P-SV complex and (ii) altered cellular foci and nodules in the livers. Methylnitrosourea induced a high incidence of benign lung adenomas which progressed to lung cancers in numbers which were of marginal significance. Thus, dormant MNU-initiated cells in the P-SV complex were activated by phenobarbital, to produce adenocarcinomas in that complex.

A model system for the in vivo determination of the thrombolytic effect of plasminogen activators.

An in vivo model system for measuring the thrombolytic efficiency of plasminogen activators was used. The formation of radiolabelled microthrombi was induced by infusion with I-125 labelled fibrinogen and thrombin. Reactive fibrinolysis was inhibited by administration of suboptimal levels of e-aminocaproic acid. The thrombolytic and subsequent fibrinolytic events were followed in the capillary bed of the lungs of anesthetized rats by external monitoring of the I-125 activity over the lung field. The model was successfully employed to demonstrate the thrombolytic effect of plasminogen activator produced by a transplanted spontaneous rat prostate adenocarcinoma cell line (PA III). The system proved to be reproducible with detection limits of 6000 I.U. using the PA-III cell line derived activator.

A fibrin specific monoclonal antibody which interferes with the fibrinolytic effect of tissue plasminogen activator.

Monoclonal antibodies to human fibrin have been prepared from stable hybridomas, obtained by fusion of a mouse myeloma cell line (NS-1) and spleen cells of Balb/c mice immunized with a suspension of human fibrin. One cell line, DG1, producing a monoclonal antibody of the IgG1, kappa subclass, reacted specifically with human fibrin (KD = 1.2 nM). Western blotting analysis indicates that DG1 crossreacts with the fibrin fragment D-dimer. Using both a chromogenic and an 125I-fibrin release assay it was illustrated that in the presence of the fibrin specific antibody the t-PA mediated generation of plasmin was significantly inhibited. An animal model system, developed to monitor thrombosis and induced reactive fibrinolysis, was used to investigate the interference of plasminogen activation, by the antibody, in vivo. This fibrin specific antibody prolonged the onset of reactive fibrinolysis in a dose dependent manner.

Effects of diphosphonate and x-rays on bone lesions induced in rats by prostate cancer cells.

Prostate adenocarcinoma-III (PA-III) cells deposited over the scapula of Lobund-Wistar (L-W) rats induced osteolytic and osteoplastic changes in that bone. The osteolytic process was prevented and interrupted by administrations of dichloromethylene diphosphonate (Cl2MDP); but the osteoplastic process, once initiated, continued. The latter process was interrupted by ionizing radiation. Treatments of PA-III-affected bones with Cl2MDP and x-rays immobilized both osteolytic and osteoplastic processes.

Comparison of resting intracoronary particulate imaging and stress thallium-201 studies.

Stress thallium-201 and resting dual intracoronary particulate imaging were evaluated in 120 patients who underwent coronary angiography. Forty of 42 patients without significant coronary disease had normal stress images and 41 had normal rest studies. Eighty-three stress perfusion defects were identified in 61 of 78 patients with coronary artery disease. At rest, 39 of these defects were resolved or improved, whereas 44 remained unchanged. The angiographic presence of collateral vessels and radionuclide evidence of blood flow distribution through them could not always be correlated as 36 angiographic collateral vessels had no regional distribution flow patterns with either method. Particulate studies demonstrated myocardial flow distribution through 25 angiographic collateral vessels and further identified seven collateralized areas not seen angiographically. The resting particulate images additionally defined flow distribution patterns in 15 instances in which the angiogram indicated two potential sources of blood supply.

Ventricular uptake during brain scanning. A case report of ventricular lymphomatosis.

Visualization of the cerebral ventricles during radionuclide brain scanning is rarely reported. A case demonstrating the lateral ventricles by brain scanning with 99mCc-stannous glucoheptonate in a patient with lymphoma is presented.

Use of microcapsules as timed-release parenteral dosage form: application as radiopharmaceutical imaging agent.

The development of a new type of parenteral dosage form is described. A system of microencapsulation was formulated which produced microcapsules containing a water-soluble core material. The basic microencapsulation system could be altered to produce microcapsules with varied timed-release characteristics. Tracer methodology was employed as a sensitive and versatile analytical tool for the development and evaluation of the microencapsulation system. The core material was labeled by neutron activation after microcapsule formulation, which eliminated the radiation hazard and contamination problems that could occur during formulation with a labeled core material. Both in vitro and in vivo testing showed that the release patterns of labeled core material could be altered and detected. The microcapsules developed have potential as a timed-release parenteral dosage form and as an organ-imaging radiopharmaceutical.