Pharmacokinetics of the 5'-triphosphates of arabinosylcytosine and 2',2'-difluorodeoxycytidine in L1210 cells.

The clinical efficacy of ara-C is limited by a rapid elimination of the active triphosphate by target cells. The nucleoside antimetabolite, 2',2'-difluorodeoxycytidine, accumulates in leukemia cells as the respective 5'-triphosphate dFdCTP. In contrast to ara-C triphosphate, dFdCTP is eliminated with biphasic kinetics that exhibit a terminal half-life that approaches the cell cycle time.

Magnetic affinity colloid (MAC) cell separation of leukemia cells from autologous bone marrow aspirates.

A colloidal suspension of Co2B with avidin irreversibly adsorbed to the surface has been used with biotinylated antibodies and lectins to eliminate specific cell populations from mixtures with peripheral blood or bone marrows. Using the monoclonal antibodies CF-1 and PM-81 with this magnetic affinity colloid (MAC), we can eliminate five logs of K562 cells from mixtures with peripheral blood or marrow cells as determined by a linear limiting dilution clonogenic assay. We have also used this separation to eliminate clonogenic leukemia cells from fresh samples of peripheral blood and bone marrow from relapsed acute leukemia patients.

Response to BCNU of spheroids grown from mixtures of drug-sensitive and drug-resistant cells.

Multicellular spheroids were grown from mixtures of rat brain tumor cells sensitive (9L) and resistant (R3) to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). As shown previously, after treatment with 3 microM BCNU, percentages of each cell subpopulation in mixed-cell spheroids were estimated with the sister chromatid exchange (SCE) assay and found to be approximately the same as percentages used to initiate spheroids. The sensitivity of 9L cells in mixed-cell spheroids treated with BCNU, estimated by changes in the number of SCEs induced by treatment, decreased as the percentage of R3 cells increased.

Epidemiologic similarities leading to etiologic hypotheses.

Analogy is a useful means of generating etiologic hypotheses which can be tested by epidemiologic, clinical, or laboratory studies. We describe how the use of analogy has furthered the understanding of three disease entities--Hodgkin's disease (HD), testicular cancer (TC), and acquired immune deficiency syndrome (AIDS). HD is probably caused by a virus of low pathogenicity with clinical expression dependent on social factors.

Severe hypertensive reactions to teniposide (VM-26) in infants with congenital leukemia.

Two cases of infants with congenital leukemia who had severe, refractory hypertensive reactions to teniposide (VM-26) are described. Patients on a 5 mg/kg twice weekly schedule of teniposide had hypertensive reactions in which their systolic blood pressure was greater than 200 mm Hg after the second dose of teniposide. Hypertension combined with myelosuppression resulted in the patient's death in one case.

Anatomy of the major lacrimal gland of rhesus monkeys (Macaca mulatta).

The major lacrimal gland of rhesus monkeys is impalpable within the fatty connective tissue of the upper lateral quadrant of the orbit. Acini of the lacrimal glands are composed of both sparsely and heavily granulated cells that histochemically resemble serous acinar cells of the submandibular salivary gland. The cytoplasmic granules are strongly periodic acid-Schiff (PAS)-positive, and some are also stained by alcian blue for acidic mucosubstances.

In vitro evaluation of difloxacin (A-56619), A-56620, and other 4-quinolones against isolates from cancer patients.

The in vitro activity of two new quinolones, difloxacin and A-56620, was compared with that of other quinolones against isolates obtained from bacteremic cancer patients. Both agents had a broad antimicrobial spectrum which included both gram-positive and gram-negative organisms. A-56620 had lower MIC values against most organisms tested than difloxacin, and its activity was comparable to that of ciprofloxacin.

The ultrastructure and immunocytochemistry of renal cell carcinoma.

The spectrum of ultrastructural features of a series of primary renal cell adenocarcinomas, including clear cell, granular, oncocytic, and sarcomatoid types, and a group of metastatic renal cell adeno-carcinomas has been studied. The contributions of electron microscopy and immunocytochemistry as adjuncts to light microscopy and histochemistry in the differential diagnosis of metastatic renal cell adenocarcinoma in various anatomic locations are reviewed.

Comparison of results of salvage therapy in adult acute myelogenous leukemia.

The results of initial salvage therapy for refractory and relapsed acute myelogenous leukemia for patients treated between 1973 and 1986 have been evaluated. There was no significant improvement in complete remission (CR) rate and survival in patients treated between 1973 and 1980, and the second group between 1981 and 1986. The remission duration was slightly longer in the second time period than in the initial time period.

Clot embolic stroke in the vertebrobasilar system of rabbits: a transfemoral angiographic technique.

Previous animal models of thromboembolic stroke have focused upon the carotid artery system. An alternative approach utilizing the vertebrobasilar system in rabbits is presented here. Left vertebral artery catheterization was accomplished relatively simply in this model using transfemoral angiographic techniques.

Diagnostic electron microscopy using fine needle aspiration biopsies.

Electron microscopy can be a valuable aid to light microscopy in the interpretation of fine needle aspiration biopsies of tumors, but considerable care in procuring and processing the specimen is necessary to recover the tumor cells and avoid altering their fine structure. Fixation followed by filtration through a cloth screen is recommended. Experience with this technique is briefly reviewed.

Ultrastructural observations on smooth muscle tumors.

The ultrastructure of a series of primary and metastatic smooth muscle tumors is reviewed. Myofilaments and other smooth muscle features were present in all primary leiomyosarcomas of the soft tissues and uterus. They were also present but were less plentiful in most of the metastatic leiomyosarcomas.

Massive Wilms' tumor: sonographic demonstration of therapeutic response without alteration in size.

The use of ultrasound to detect a response of massive Wilms' tumor to preoperative chemotherapy is demonstrated. Anechoic areas appearing during treatment are highly suggestive of response even in the absence of a reduction in size.

Distribution, expression and germ line transmission of exogenous DNA sequences following microinjection into Xenopus laevis eggs.

We analysed the fate, expression and germ line transmission of exogenous DNA which was microinjected into fertilized eggs of Xenopus laevis. DNA was injected into fertilized eggs within 1 h following fertilization. The injected DNA was dispersed around the site of injection and became localized to cleavage nuclei by stage 6.

Acquired immunodeficiency syndrome.

The acquired immunodeficiency syndrome (AIDS) was recognized as a distinct clinical entity in 1981 and was characterized by unexplained opportunistic infections and an aggressive form of Kaposi's sarcoma. High risk groups for contracting AIDS include homosexual men, parenteral drug users, hemophiliacs, recipients of blood and blood products, and heterosexual contacts of such individuals. Immunologic abnormalities associated with AIDS include lymphopenia, functional T-cell deficits, B-lymphocyte defects, and various serologic abnormalities.

Hyperbaric oxygen and radiobiology of a C3H mouse mammary carcinoma.

A series of radiation dose-tumor control response assays was performed on the first-to-fourth generation isotransplants of a C3H/J mouse mammary carcinoma for radiation administered under four different conditions: hypoxia, a clamp across the root of the tumor-bearing part for 1 minute before treatment; air, animal respiring air at one atmosphere of pressure; O2 30 or 44 psi, animal respiring pure oxygen at 30 or 44 psi for 15 minutes before and during local tumor irradiation. When radiation was administered as a single dose (v = 1) to 250 mm3 tumors, high pressure oxygen was only modestly effective in reducing the tumor control dose (TCD50); TCD50 hypoxia/O2 30 psi and TCD50 hypoxia/O2 44 psi were only 1.2 and 1.