A glycoprotein: galactosyltransferase activity in the ascitic fluid and serum of mice with the YC8 tumor]

Tranfer of (14C)-gal from exogenous UDP(14C)-gal has been demonstrated with ovomucoid as glycoprotein acceptor in ascitic fluid sera from Balb/c mice bearing isogenic YC8 tumor. Transfer exists without ovomucoid, in great ratio in ascitic fluid and in sera from ascitic mice too, showing occurrence of endogenous acceptors, the origin of which has to be proved.     

Demonstration of N-acetylgalactosaminyltransferase activity in the murine lymphoma YC8]

The N-acetyl-galactosaminyltransferase activity has been studied in the biological fluids of YC8-lymphoma bearing Balb/c mice. It is enhanced during tumor development from 1 to 30 times in peritoneal fluids and from 1 to 10 times in sera. This activity is nil in urines. Optimal requirements for activity have been determined. Results suggest the existence, during tumor process not only of an enhancement of enzymatic activity, but also of a new molecule synthesis, molecules which are endogenous acceptors for the enzyme.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution. The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

Summary A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution.The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.Supported by the United States Department of Energy and National Institutes of Health Grant P41-RR01315.     

Cytotoxicity of mouse peritoneal cells after alloimmunization]

CBA Mice were immunized by two intraperitoneal injections of 30 X 10(6) DBA/2 or C57BL/6 spleen cells at days--12 and--2. Peritoneal cell population was obtained at day zero by washing the peritoneal cavity of Mice. Adherent cells were then separated using a 2 hrs. incubation in "Falcon" plates followed by washing. This macrophage-rich peritoneal cell population was found nonspecifically cytotoxic against 51Cr labeled tumoral target cells: P815 X DBA/2 mastocytoma cells, EL4 X C57BL/L lymphoma cells and spontaneous lymphoma AKR cells (same H--2k as CBA). This adherent peritoneal cell cytoxicity was demonstrated after 24 hrs. incubation with the target cells. It was found in nonspecific combination as well as when using target cells syngeneic to the donor. These findings suggest that adherent peritoneal cell cytotoxicity could be at least partly due to macrophages and result from factor (s) released by sensitized lymphocytes in vivo in the same way as has been previously demonstrated in vitro.     

Inhibition of transplanted mouse tumors by heterologous transfer RNA

Summary Injections of yeast tRNA to C57BL mice decreased takes and inhibited growth of syngeneic transplanted tumors. Mice remaining free of tumors as result of this treatment failed to develop tumors after challenge with 5×10⁴ cells of the same tumor.This work was supported in part by a grant from the Stanley Johnson Foundation, Berne, Switzerland.     

Vascular permeability in malignant disease

Summary Experimental demonstration that vessels draining large tumours are impermeable to cellular elements. Thus the pulmonary vessels of animals bearing large, primary (other than gastro-intestinal) cancers can become impermeable to tumour emboli. This imperviousness prevents the establishment of secondaries in the lung and promotes the transpulmonary passage of tumor cells. This phenomenon may account for the development of paradoxical metastases.     

Renewal of noradrenaline in different zones of the central nervous system of inbred mice strains and their recombinants]

A good correlation exists between the learning capacity and norepinephrine metabolism in the neocortex of C57 and Balb inbred Mice strains, as well as their F1 hybrids and seven recombinant inbred strains derived from their cross. The animals with a better learning performance are characterised by low levels of norepinephrine, as well as a slow metabolic rate of this neurotransmitter in the cortex. Such a correlation has not been found to exist in the other cerebral regions studied.     

Antiinflammatory reaction associated with murine L1210 leukemia

Summary Mice bearing L1210 leukemia did not show impaired humoral or cellular immune response to antigenic stimulation during the early stage of the tumor, and a depressed response was noted only in the terminal stage. L1210 cells were shown to suppress inflammatory reaction in vivo.Supported in part by USPHS research grant No.5-01-RR05-352-12, and by theIndependent Order of Foresters, San Bernardino District 3208. We acknowledge the valuable assistance ofJudith Johnson andJames Tan in this project. Histopathological examination byDick H. Koobs is appreciated.     

Production of monoclonal anti-Schistosoma mansoni antibodies. Preliminary study of their biological activities]

Monoclonal antibodies against Schistosoma mansoni have been produced by fusion of splenic lymphocytes from S. mansoni infected Rats and P3-X63-Ag8 BALB/c cells. In vitro and in vivo studies of the biological activities of these antibodies have led to the identification of IgE antibodies with a high reaginic activity and antibodies which in a complement dependent or eosinophil dependent system were shown to have a marked cytotoxicity for schistosomula in vitro. This methodology seems to open new perspectives for the study of antibody function in immunity against parasites as well as for the isolation of the corresponding target antigens.     

Transfer and induction of delayed hypersensitivity to methylated bovine serum albumin in the absence of adjuvant]

Delayed hypersensitivity to methylated bovine serum albumin may be induced in Mice without adjuvant, by injecting the antigen either with sensitized T lymphocytes, or by injecting just the antigen in Mice preptreated with Cyclophosphamid.     

Alloantigens directed by the SL-A region control the mixed lymphocyte reaction in swine]

Immunizations between a pig bearing a recombined SL-A haplotype and related animals revealed serological defined antigens under the MLR region control. These antigens seemed to be carried by all types of lymphocytes so far studied, but with large quantitative differences. The blood nonadherent on nylon fiber lymphocytes carried very few antigens and platelets none at all. The data are compatible with the assumption that these newly discovered antigens are equivalent to the mouse Ia antigens.     

Potentiation of the biological activities of daunomycin and adriamycin by ascorbic acid and dimethylsulfoxide

Summary L-Ascorbic acid (0.57 mM) and dimethylsulfoxide (14.1 mM) were found to potentiate four times the antibacterial activities of daunomycin and adriamycin in theStaphylococcus aureus test. This effect, however, could not be demonstrated against eukaryotic cells and leukemia P388 in mice. The authors thank Dr A. Maráz, Department of Microbiology, J.A. University, Szeged, and Dr Zs. Somfai, Institute of Oncology, Budapest, for collaboration in the experiments with yeast and tumor cells.     

Existence of several non-specific recognition systems in macrophages]

Rat peritoneal cells were made to bind five particle species: immunoglobulin-coated Sheep red cells, glutaraldehyde-treated Sheep red cells, latex beads, leishmania and tumor cells. The dependence of binding on various physico-chemical parameters was studied. The binding of latex beads or Leishmania was not inhibited by cold (4 degrees C), sodium azide, cytochalasin B and ethyleneglycol or dimethylsulphoxide. The binding of immunoglobulin-coated Sheep red cells was unaffected by cold and azide, but it was inhibited by cytochalasin B, ethyleneglycol and dimethylsulphoxide. The binding of glutaraldehyde-treated Sheep red cells was inhibited by cold, azide and ethyleneglycol, but it resisted cytochalasin B and dimethylsulphoxide. The binding of tumor cells was inhibited by azide, cytochalasin B, ethyleneglycol and dimethylsulphoxide. It is concluded that: (a) macrophages are endowed several sets of non-specific binding structures that are differently affected by physico-chemical parameters, which provides a simple way of characterizing them; (b) the expression of a given binding structure on the macrophage membrane is modulated by metabolic inhibitors; (c) some lymphocytes were able to bind tumor cells or Leishmania. Thus, lymphocytes and macrophages might share some non-specific adhesive structures.     

Kinetics of decrease and apparent transformation of fluorescence spectra of benzo(a)pyrene absorbed by living cells: case of lymphocytes and macrophages]

A home made microspectrofluorimeter is used in order to follow the decrease of fluorescence intensity of Benzo(a)Pyrene after its absorption by single living cells. The kinetics look to be a first order one; fluorescent metabolite can be detected when peritoneal macrophages of Mice are used but not with human periferic lymphocytes pretreated with mitogens.     

Kinetics of the appearance of HLA-DR antigens on human alloactivated T lymphocytes and the demonstration of new antigenic determinants

By studying serologically the appearance of HLA-DR determinants on T lymphocytes activated by a mixed lymphocyte culture, we have been able to demonstrate the existence of a new class of antigenic determinants distinct from classical HLA-DR antigens. Indeed, some monospecific anti-DR sera were cytotoxic from some alloactivated T cells, though not directed against their HLA-DR specificity. The absorption of these anti-sera on B lymphocytes bearing the HLA-DR antigen against which they were directed, did not remove their reactivity on alloactivated T lymphocytes. The absorption of the same anti-sera on activated T lymphocytes did not affect their anti-DR reactivity. This study shows the existence of new antigenic determinants expressed by T lymphocytes during their activation: alloactivated T lymphocyte antigens (AATL).     

Environmental temperature and the growth ofTaenia crassiceps cysticerci in mice

Summary Mice kept at low (5±1 °C) and high (35±1 °C) temperature harboured significantly lessTaenia crassiceps cysticerci than controls kept at 21±1 °C. This effect was more pronounced in heat-stressed than in cold-stressed animals and more in males than in females.     

Developmental and ageing changes in aminopeptidase activities in selected tissues of the rat

Aminopeptidase activities, assayed as arylamidase activities, were investigated in selected tissues of 1, 6, 12 and 24-month-old rats. The enzyme activities were found to have a heterogeneous distribution and age-related changes were observed. The highest levels of soluble arginyl-aminopeptidase activity were detected in brain homogenate at all the studied ages, whereas membrane-bound activity presented the highest levels in brain and kidney in the four ages tested. Aspartyl-aminopeptidase activity was detected mainly in the particulate fraction of kidney at all four ages. In 1, 6 and 12-month-old animals, soluble aspartyl-aminopeptidase activity was also higher in the kidney than in the rest of the tissues, whereas in the group of 2-year-old rats, the highest levels were found in both kidney and liver. Age-related changes were observed in all the studied tissues and for all the assayed enzymatic activities. In general, the maximal levels were detected in both the youngest and the oldest animals, and the minimal ones in 6 and 12-month-old rats. However, in the adrenals, the soluble and membrane-bound arginyl-aminopeptidase activity was higher in 6-month and 2-year-old rats than in 1-month and 12-month-old rats. These changes may reflect the functional status of the susceptible endogenous substrates of aminopeptidases.     

Biological activities of pure prostaglandins

Prostaglandins, the hydroxy unsaturated C20 fatty acids, are found throughout the body and have an equally wide range of biological activities. Prostaglandins are known to: 1) stimulate uterine contraction; 2) inhibit spontaneous contraction of the rabbit uterus; 3) inhibit the respiratory smooth muscle of different animals; 4) lower systemic arterial blood pressure when injected intravenously; 5) stimulate contractions in isolateral segments of intestinal smooth muscle of most species investigated; 6) produce transient sedation when intravenously injected in cats, and 7) inhibit lipolysis induced by catechal amines, corticotrophin, glucagon and thyroid stimulating hormone. The inhibitory and excitatory effects of prostaglandins may each have a physiological importance at different sites. Current state of knowledge of the distribution, metabolism and actions of the prostaglandins is still fragmentary. The functional significance of the prostaglandins is yet to be determined.