Biomedical subjects

W P Drake

Publications and source records attributed to W P Drake.

14 recordsLinked to original sources

PubMed1977

Application of laser cytometry to the analysis of immunologically induced in vitro lymphocyte responsiveness.

This study defines an assay (laser analysis) that is a significant advance in our ability to quantitate and analyze immunologically induced in vitro lymphocyte responsiveness. Laser analysis is demonstrated to parallel radionucleotide incorporation (3H-thymidine) in terms of kinetic pattern, dose response characteristics, and statistical accuracy while exeeding radionucleotide incorporation in sensitivity. Direct quantitation of lymphocyte responsiveness, in terms of cellular proliferation, disclosed that substantial numbers of small lymphocytes were produced during in vitro stimulation with mitogen (concanavalin A) or antigen (streptokinase-streptodornase) in addition to the expected increase in lymphoblasts. The magnitude of this "total cellular response" (lymphocytes plus lymphoblasts) was found to be similar for antigen and mitogen stimulation, a finding not suggested by routine radionucleotide incorporation or morphological assays.

Concanavalin A↗

PubMed1976

Latent homology of murine lymphoid antigens revealed through the complement mediated absorption of xenogeneic antiserum.

Xenoantiserum against C57BL/6 mouse spleen cells was produced by immunization of rabbits. Such antiserum displayed cytotoxic activity for several strains of mice. Standard "in vitro" absorption removed species specific antibody revealing antibody directed against the C57BL/6 strain. When the xenoantiserum was absorbed with DBA/2 spleen cells in the presence of complement, the binding of anti-C57BL/6 was increased. Such data suggest that xenoantibodies directed against spleen cells possess a broader capacity to react with cross-strain lymphoid antigens than previously described.

Animals↗

PubMed1976

A proper sequence for the treatment of B16 melanoma: chemotherapy, surgery, and immunotherapy.

The therapeutic effectiveness of surgery, chemotherapy, and immunotherapy alone and in combination were studied in the B16 melanoma model. The sequence of chemotherapy and immunotherapy as adjuvants to surgery proved important: Chemotherapy was significantly better when given before surgery; immunotherapy was more effective when delivered after surgery. The most effective therapeutic regimen was a combination of all three modalities: a single course of chemotherapy preceding surgery followed by immunotherapy.

Animals↗

PubMed1976

The age-dependent efficacy of polyadenylic-polyuridylic acid therapy upon the development of spontaneous leukemia in AKR mice.

The synthetic double-stranded polynucleotide, polyadenylic-polyuridylic acid, has been shown to increase the long-term survival of AKR mice. In order to determine whether this effect was age dependent, polyadenylic-polyuridylic acid was administered to AKR mice starting at 2, 4, 6, or 8 months of age. The best therapeutic effect was achieved when polyadenylic-polyuridylic acid treatments were begun at 2 months of age, and there was no beneficial effect when begun at 8 months of age.

Age Factors↗

PubMed1976

In vivo decomplementation of guinea pigs with cobra venom factor and anti-C3 serum: analysis of the requirement of C3 and C5 for the mediation of endotoxin-induced death.

Guinea pigs were decomplemented by administration of cobra venom factor and goat anti-C3 serum in order to determine whether endotoxin-induced death could be prevented. The combined use of both reagents resulted in the complete elimination of all serum C3 and C5 hemolytic activity. This yielded, however, a shortened rather than extended longevity following endotoxin challenge. The mixing of endotoxin in vitro or in vivo with serum of animals already partially depleted of C3 resulted in no further activation of this component, further suggesting that the interaction of complement with endotoxins does not relate to mortality in animals following endotoxin challenge. Thus, although it has been demonstrated that complement components aid in the detoxification of endotoxin, the present data show that the C3 and C5 components are not mediators of endotoxin-induced death.

Animals↗

PubMed1975

Elevated ribonuclease activity in the thymus and white blood cells of genetically cancer prone mice.

Ribonuclease activity in cell-free thymus homogenates was elevated for five strains of mice genetically predisposed toward leukemia or reticulum cell neoplasms (AKR, C58, PL, RF, and SJL). Such increased activity was directed against polyuridylic acid and was observed in 8-wk old mice, well before the onset of neoplastic transformation. Similarly, white blood cell ribonuclease activity was elevated in mice of the strains AKR, C2H/He, PL and RF. Statistical analysis indicated that such elevated activity in these strains related to their high incidence of spontaneous neoplastic disease. Elevated ribonuclease activity thus represents a new biochemical marker relating to the genetic propensity of some strains of mice to die prematurely of spontaneous neoplasia.

Animals↗

PubMed1975

A white blood cell RNase assay for the possible monitoring of malignancy.

The RNase activity observed in the sera of leukemic guinea pigs was compared to that observed in white blood cell (WBC) lysates of the same animals. The WBC-associated RNase activity directed against polyuridylic acid decreased with the progression of neoplastic disease, though serum RNase activity remained unchanged. With certain forms of cancer, therefore, variations in cell RNase may be more sensitive markers than changes in serum RNase for the evaluation of the progression or regression of disease.

Animals↗

PubMed1975

Abnormal profile of human nucleolytic activity as a test for cancer.

Serum samples from patients with various malignancies including acute nonlymphocytic leukemia (ANLL), brain tumor (BT), Hodgkin's disease (HD), and non Hodgkin's lymphoma (NHL) were evaluated for nucleolytic activity against six synthetic polynucleotides: polyadenylic acid, polyuridylic acid, polycytidylic acid, polyguanylic acid, polyadenylic-polyuridylic acid, and polyguanylic-polycytidylic acid; The enzyme activity was determined spectrophotometrically by following the degradation of substrate to acid-soluble nucleotides. Most patients had elevated serum RNase activity at the 95% confidence level when compared to 30 controls. Included in this group were 67% of patients with ANLL, 46% of patients with BT, 73% of patients with HD, and 67% of patients with NHL. These data confirmed the earlier suggestion that elevated serum nuclease activity is found in patients with neoplastic disease. However, whether or not a serum was identified as abnormal depended on the substrate used in the assay; this underscored the need to test samples against a variety of polynucleotides. Alterations in serum nucleolytic activity represent an important marker of neoplastic disease and can serve as the basis for a useful clinical screening device.

Brain Neoplasms↗

PubMed1975

The dependence of successful immunotherapy on adequate tumor burden as shown by the treatment of AKR leukemia with poly A-poly U.

The therapeutic efficacy of polyadenlyic-polyuridylic acid (poly A-poly U) on the transplantable AKR leukemia varied with the dose of tumor cells implanted. The greater the number of AKR tumor cells injected into 8-week-old AKR mice free of clinical evidence of cancer, the greater the effect of poly A-poly U in mediating host immunologic control of the tumor. Poly A-poly U was either ineffective or could enhance tumor growth when smaller doses of tumor cells were transferred. The efficacy of an immune adjuvant depended on a tumor burden affording optimum host responsiveness. This does not necessarily arise in the host bearing minimal tumor burden.

Adjuvants, Immunologic↗

PubMed1975

Alterations in ribonuclease activities in the plasma, spleen, and thymus of tumor-bearing mice.

Six transplantable murine tumor models were evaluated for changes in RNase activity. This study was conducted with spleen and thymus homogenates, as well as with plasma collected from tumor-bearing mice. Nuclease activity directed against the synthetic substrates, polyadenylic acid, polyuridylic acid, and polycytidylic acid, was measured and the data obtained for tumor-bearing animals were compared to their normal counterparts. Elevated activity against polyuridylic acid was observed in the plasma of all tumor-bearing mice. Although not as all inclusive, RNase levels in both the spleen and thymus were generally altered as well. The observance of unilateral changes in nuclease activity directed against the synthetic substrates demonstrated that, in most cases, two or more enzymes were being detected. The assay may have some eventual value in the monitoring of cancer

Adenocarcinoma↗

PubMed1975

Enhancement of spontaneous C3H/HeJ mammary tumorigenesis by long-term polyadenylic-polyuridylic acid therapy.

Female C3H/HeJ mice received weekly s.c. injections of 2 mg polyadenylic-polyuridylic acid. Therapy was initiated at either 2 or 9 months of age. In both cases, poly-adenylic-polyuridylic acid-treated animals developed the spontaneous mammary carcinoma associated with this strain more rapidly. Because the opposite result was formerly observed for AKR spontaneous leukemia, the data indicate the polyadenylic-polyuridylic acid has no generalized antineoplastic effect upon spontaneous tumors genetically associated with specific murine strains.

Animals↗

PubMed1975

The kinetics of the interaction of heterologous anti-tumor serum and heterologous complement in non-tumor bearing mice.

The persistence of heterologous antitumor serum in the periphery of normal, non-tumor bearing mice was analyzed following intravenous, intraperitoneal, and subcutaneous injection. Intravenous injection of guinea pig complement subsequent to antibody administration resulted in the immediate disappearance of tumor-specific antibody from the periphery. Such studies suggest that appropriate therapy by the passive administration of antiserum requires the initial administration of antibody to allow for preferential binding to tumor-specific antigens followed by the subsequent injection of complement to mediate tumor cytolysis.

Animals↗

PubMed1975

Complement-mediated alteration of antibody specificity in vivo.

The simultaneous injection of heterologous anti-EL4 lymphoma serum and complement results in the rapid disappearance of such antibody from the periphery of non-tumor bearing mice. However, this phenomenon is only observed when a complement source capable of mediating the lysis of EL4 cells sensitized with such heterologous antibody is used. This complement mediated enhancement of anti-tumor antibody absorption was observed in vivo for three strains of mice. Omission of complement or the use of genetically deficient complement sources resulted in no effect on circulating antibody titer when compared to the titer of heterologous anti-tumor antibody observed in the periphery when injected alone. Exogenous complement did not enhance the clearance of heterologous anti-tetanus toxin serum, thereby suggesting that the increased absorption of anti-EL4 in vivo is not related simply to the enhanced clearance of foreign gamma-globulin. Confirmatory evidence of the role of complement in altering anti-tumor antibody specificity in vivo was obtained in a guinea pig tumor model as well. The data suggest that anti-tumor serum shown to be relatively specific for the tumor cell gains additional specificity in the presence of functional complement and consequently manifests avidity for cross-reactive determinants previously thought to be unrelated.

Absorption↗

PubMedDate not supplied

Alteration of cellular ribonucleases associated with murine oncogenic virus infection.

The ribonuclease activity of peripheral lymphocytes from Balb/c mice was studied at various intervals subsequent to infection of mice by oncornavirus. Lymphocytes from mice infected with Friend leukemia virus possessed elevation of RNase activity within 8 days subsequent to infection. Balb/c mice infected with Moloney sarcoma virus demonstrated an analogous elevation of RNase activity with 7-9 days postinfection. Diminishment of cellular RNase activity occurred in the Friend leukemia model concomitant to the occurrence of significant numbers of erythroblasts in the peripheral blood, while ribonuclease activity in lymphocytes from mice infected with Molney sarcoma virus returned to normal 1-2 weeks subsequent to host rejection of tumor. It is concluded that elevation of RNase activity within the lymphocyte represents an early event in oncogenic viral infection within these two tumor models. The possible meaning of elevation of RNase activity is a target (the lymphocyte) not predestined to undergo neoplastic transformation is discussed.

Animals↗