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Immunobiology of paediatric intracranial tumours. A preliminary report.

Preliminary findings in the evaluation of the immune response of children with primary neoplasms of the CNS, mainly medulloblastomas, are reported and discussed. A broad scheme for the monitoring of B- and T-cell-dependent immunity and of delayed hypersensitivity reactions in this type of patient is presented. The most important immunobiological findings are discussed. Special attention is given to the striking failure of the T-cell-dependent pool (currently identified by "active" RFC and blastigenesis tests) and to the remarkable decrease of hypersensitivity reactions (depressed skin-test response), both of which seem to be related to the degree of malignancy of the tumour. A very peculiar feature, i.e., the appearance of cells with natural cytotoxic activity, is dealt with in some detail. Our present knowledge concerning the immunobiology of primary CNS neoplasms is still very incomplete, but seems to suggest a possible role for immunotherapy in paediatric neurosurgery.

B-Lymphocytes

Assessment of immunobiological effects induced by chemicals, drugs or food additives. I. Tier testing and screening approach.

The indications of immunologic dysfunction following low level exposure of rodents or even man to certain chemicals and drugs have raised concern regarding methodology and approaches for routine assessment of immunobiological effects. The immunogiological effect observed may either indicate impaired immunopotentiation or hypersensitization. The assays selected for testing should be relevant to the human experience and adaptable to certain practical considerations such as cost, reproducibility of data, ease of performance and application to routine toxicology studies. Using these considerations, a tier approach was proposed consisting of assays for screening for immunologic effects (Tier I) and assays to help define the mechanisms responsible for the immunobiological effects observed (Tier II). A tier of assays was also proposed for measuring the sensitization potential of certain compounds. Certain assays from the screening tier were assembled into a hypothetical and practical test battery to screen for immunological effects of a chemical with potential immunosuppressive properties. Information provided by this test battery should provide a reasonable and sensitive data base from which a standard of evaluation could be made regarding the safety of the test (1) compound.

Animals

Biochemical, immunochemical and immunobiological properties of a chloramphenicol-resistant Salmonella typhi strain isolated in Mexico.

The authors have compared the biochemical, immunochemical and immunobiological properties of a chloramphenicol-resistant S. typhi strain isolated during the typhoid fever epidemic in Mexico of 1972 and those of a chloramphenicol-sensitive strain (S. typhi Ty2). They have found no difference in the chemical composition of the two strains. The immunobiological investigations have shown, that the chloramphenicol-resistant strain contains less Vi antigen, it is less virulent on mice, and its active and passive mouse-protective ability is lower than that of the chloramphenicol-sensitive S. typhi Ty2 strain. These findings supported by the result of the electrophoretic analysis suggest that the chloramphenicol-resistant strain is a VW strain, while the chloramphenicol-sensitive strain is a full V strain; the quantitative difference found between the immunogenicity of the two strains to the advantage of the chloramphenicol-sensitive strain may probably be explained by this fact. On the basis of their immunological investigations the authors are of the opinion, that vaccines prepared from chloramphenicol-sensitive S. typhi strains (provided these are full V strains, as e.g. the S. typhi Ty2 strain) will protect most likely also man against infection due to chloramphenicol-resistant S. typhi strains.

Agglutination Tests

The control of immunobiological preparations in Hungary and its importance for national vaccination programmes.

In Hungary the control of immunobiological preparations has been regulated by legal orders since 1938. In the meantime the pertinent rules have been modifed several times, to keep them abreast with current development. The authority of state control has been vested into the Vaccine Control Department of the National Institute of Public Health (OKI), which in this capacity has maintained an intensive collaboration with the producer of immunobiological preparations, the HUMAN Institute of Serobacteriological Production and Research (HUMAN). As a result, several important vaccine preparations (pox, DPT, DT, tetanus, typhoid and BCG vaccines) employed in compulsory immunization programmes have been improved considerably in respect of safety and efficiency, on the basis of laboratory tests, controlled field trials and epidemiological observations, described in detail in this review.

BCG Vaccine

Immunobiology of head and neck cancer: basic concepts.

Patients with squamous cancer of the head and neck have unique perturbations of the immune system. These patients have marked depression of cellular immunity even in the early stages of disease. The known facts about the immunobiology and the immunodeficiencies that commonly occur are discussed. Also reviewed are the relationships of the immunologic deficits to stage of disease, to prognosis, and to the suspected etiologic factors of smoking, alcoholism, and malnutrition. Highlights are given of current immunotherapeutic trials. To date, most of the successful efforts in both immunologic research and immunotherapy of head and neck cancer have dealt with general, rather than specific, immune reactions. Further development in the area of specific immune responses may permit more meaningful measurements of tumor-specific reactions, thus yielding useful tools for immunodiagnosis as well as providing more effective and precise methods of immunotherapy.

Carcinoma, Squamous Cell

Commentary on the immunobiology of bladder cancer.

This review is an attempt to integrate the conflicting studies that constitute the literature on immunobiology of bladder cancer and to indicate areas that need further investigation. It is clear that immune reactivity directed at antigens expressed on bladder cancer cells and general host immunologic competence decline with progressive tumor growth. This immunodepression correlates with patient prognosis, even within a given stage of disease. The mechanisms underlying this decline in host immune reactivity are poorly understood. A better understanding of these mechanisms may provide fundamental insight into the host-tumor relationship that possibly could be exploited for preventive, diagnostic and therapeutic purposes.

Animals

Immunobiology of heterotransplanted human tumors in nude mice.

The immunobiology of heterotransplanted human tumors was investigated following transplantation into nude mice of human bronchogenic, colon, rectal, ovarian, gastric, endometrial, vaginal, bladder, renal, esophageal, embryonic cell, pancreatic, and breast carcinoma, as well as fibrosarcoma, rhabdomyosarcoma, malignant melanoma, astrocytoma, Wilm's tumor, endometrial hyperplasia, and hydatidiform mole. Several of these tumors were passaged up to 15 generations. During these passages no changes in latency period for tumor development or in histology were noted. There were significant differences between several tumors in the minimum number of cells required for successful transplantation; such differences were independent of the basic biologic aggressiveness of the individual tumors. Nude mice that received transplants of fibrosarcoma and endometrial carcinoma had increased serum IgM and numbers of spleen cells and complement receptor lymphocytes. No such changes were noted for mice that received transplants of malignant melanoma, In contrast, there were no apparent differences in the responses of nude mice, who were given transplants of human tumors, to be T-cell mitogens concanavalin A or phytohemagglutinin or in the number of theta-bearing spleen cells. The success rate for transplantation was significantly improved when explants, rather than single-cell suspensions, were performed. Tumors transplanted to nude mice derived from strictly homozygous matings behaved like tumors transplanted to mice born of heterozygous mothers. Finally, despite the dramatic size of subcutaneous tumor nodules, there were no examples of invasion or distant metastases.

Animals

Immunobiology and species distribution of Mycobacterium tuberculosis antigen 5.

The immunobiology and mycobacterial species distribution of immunoabsorbent affinity chromatography-purified Mycobacterium tuberculosis antigen 5 have been studied. In delayed hypersensitivity skin tests, antigen 5 was nearly equipotent with tuberculin-purified protein derivative in sensitized guinea pigs. In vitro, antigen 5 was capable of stimulating the production of migration inhibitory factor by cultured lymphocytes from sensitized guinea pigs and humans. Antigen 5 stimulated thymidine incorporation by cultured guinea pig lymphocytes but did not stimulate thymidine incorporation by cultured human lymphocytes. Although erythrocytes were readily sensitized with antigen 5 for passive hemagglutination, their use did not offer any advantage over previous hemagglutination techniques for the serodiagnosis or evaluation of patients with tuberculosis. By immunoelectrophoresis and immunodiffusion, antigen 5 was readily identified in culture filtrates of 10 strains of M. tuberculosis and M. bovis but not in those of 30 strains of 12 other myobacterial species.

Animals

[Immunobiological means of identifying hypersensitivity to anesthetics and adjuvants].

The diagnosis of hypersensitivity to anesthetics and adjuvants is based chiefly on immunobiological tests which involve:-sensitized lymphocytes; -IgE or IgG antibodies; -sensitized target cells; -determination of chemical mediators. Comparison between these different methods is only possible for techniques involving the sensitized lymphocyte, such as the LTT and EA rosettes for examples, or T.D.B.H. and liberation of histamine. Comparison between the LTT and RAST is difficult, since the first technique investigates the sensitized lymphocyte while the second involves radio-immune antibody assay. An attempt to establish a correlation between these two types of methods is difficult but they can, however, complement each other.

Adjuvants, Pharmaceutic

The immunobiology of skin cancer.

The immunobiology of skin cancer was studied with thymus-dependent lymphocyte (T cell) levels (an in vitro measure of cellular immunity), with lymphocytic infiltration (LI) of the tumor (an in vivo measure of host-tumor relationship), and with HL-A typing (a genetic measure of histocompatibility). The T cell levels in preoperative patients with squamous (SCC) and basal (BCC) cell carcinoma were significantly lower than in the non-cancer control population (normals). The T cell levels were significantly lower in patients with large tumors than in those with small tumors. The T cell levels remained significantly low in patients cured of large tumors, but were normal in those cured of small tumors. Patients with Bowen's disease not only had T cell levels significantly lower than normal (as a group), but there was also a significant increase in the number of patients who had T cell levels less than two standard deviations below the normal mean. This may signify that they have a greater risk of developing a second kind of malignancy elsewhere. There was a direct correlation between the degree of lymphocytic infiltration (LI) of the tumor, the tumor size, and the T cell level. Small, well-localized tumors had a marked LI and high T cell levels--while the large, deeply invasive tumors had a minimal, or absent, LI and low T cell levels. The presence of HL-A antigens 1 and 8 correlated both with a tendency toward large tumors and with low T cell levels. This may represent the association of a human immune response gene with the human histocompatibility locus. Possibilities for the application of these findings in the clinical management of skin cancer are discussed.

Adult

[Asymmetry of brain lesions and immunobiologic reactivity].

The authors compare some clinico-psychopathological traits in the development and frequency of detected antibrain antibodies and allergical states in epilepsy with a different lateralization in the hemispheres. In a sinistral localization of the lesion there is a significant increase of an unfavourable development of the disease and a more frequent detection of antibodies to the homologous brain. In a dextral localization there is a relatively favourable development of the basic disorder. The authors discuss the influence of the sex factor on the immunobiological indices and the lateralization of the hemisphere. A theory is suggested that the left and right hemispheres are involved in different ways in the different links of immunity, and their pathology may provoke different changes in the body reactivity.

Autoantibodies

[Comparative evaluation of studies of the action of different levels of hypoxia on the human immunobiological status].

The effect of hypoxic hypoxia on the specific factors of immunity of 16 test subjects was studied during their 30-day exposure to an altitude of 2100-4200 m above the sea level in the area of the Elbrus mountain. In order to differentiate the effect of hypoxia per se from that of other factors typical of highlands, five runs of altitude chamber experiments were carried out. In each run the test subjects were 10 times lifted to altitudes of 3200 m, 4200 m and 5200 m. The chamber experiments were performed on 28 test subjects, aged 26-46. During an exposure to an altitude the test subjects did two or three times exercises of 450-900 kgm/min on a bicycle ergometer. The experimental findings show that hypoxic hypoxia brings about consistent changes in the immunobiological status of man that are directly correlated with the level of hypoxia. These changes include a decline in the acquired antiviral and antitoxic immunity activation of the autoimmune process and an increase in the phagocytic activity of neutrophils. Our results suggest optimal profiles of the hypoxic effect to which test subjects should be exposed during mountain training for a specific occupational activity.

Acclimatization

Immunobiology of primary neoplasms of the C.N.S. Preliminary results.

A preliminary report on the immunological monitoring of primary intracranial neoplasms is presented. The most important findings concerning B-cells and T-cells mediated immunity and delayed hypersensitivity reactions in this kind of patients, are discussed. Among the fairly significant immunobiological pictures, the Authors stress the "normal behaviour" of the B-cells dependent pool, the undebatable depression of the delayed hypersensitivity reactions, and the noticeable failure of the T-cell dependent pool, particularly marked in malignant gliomas, which are also characterized by the presence of cells with natural cytotoxic activity.

Brain Neoplasms

[Action of qualitatively varied proteins in the ration on aspects of the immunobiological reactivity of the body of white rats].

For 37--48 days the action of qualitatively different proteins (caseine jellatine) on some factors of the immunobiological reactivity of growing albino rats of the Wistar lineage was studied. A decline of the body mass and hypoproteinemia maintained on a diet with jellatine by comparison with animals with corresponding factors receiving caseine was revealed. In the spleen, mesenteric lymph nodes and in the small intestine layer proper in rats given a diet with jellatine a reduced number of plasmatic cells and also of the lymphoid series in the epithelial layer of the small intestine villi was disclosed. These animals failed to demonstrate the presence of specific antibodies 3 weeks after immunization with diphtherial anatoxin, whereas the heterohemagglutinines titre was rising. In animals kept on a diet with caseine the proportion of the heterohemagglutinines production and of specific antibodies had a reciprocal character, which manifested itself in a hefty depression of the agglutinines biosynthesis to sheep erythrocytes with an accruing titres of antidiphtherial antibodies.

Amino Acids

[Immunobiological "Allassotherapy" in sarcoidosis. Method and results (author's transl)].

Immunobiological allassotherapy is performed with subcutaneous injections of a mixture of old tuberculin and blood of a healthy donor of the same blood group who is highly sensitive to tuberculin and additional BCG injections. The results and experience over 15 years with this treatment show the advantages of this method in a series of patients with proved resistance to therapy and a poor prognosis compared with methods previously possible.

Adult

[Characteristics of streptomycin distribution and binding in the body of rabbits depending on their immunobiological state].

Some regularities of distribution and binding of streptomycin in the blood, organs and tissues of immunized rabbits werer studied. The leveles of the bound and free antibiotic in ther were determined. It was found that the immunobiological state of the rabbits had a definite effect on the distribution character and binding of streptomycin with proteins and cells in the animal organs and tissues. These changes were most pronounced in the organs and tissues of lymphoid and hematopoietic systems, the cells of which are indirect active participants of the immunity formation. As a result of proliferation of these cells the antibiotic was accumulated in higher amounts and bound more actively especially in the thymus gland and bone marrow, the central organs of the immunological reconstruction of the host. The studies are indicative of the presence of interaction between immunogenesis, distribution and binding of streptomycin in immunized animals.

Agglutinins

[Brucellosis protective antigen, its chemical and immunobiological characteristics].

The data on brucella nontoxic protective antigen without any sensitizing properties isolated from the cell wall of brucella are presented. The antigen had a marked protective effect against the experimental infection for 3-4 months after a single immunization of guinea pigs.Molecular heterogeneity of the antigen, which is mainly a protein-polysaccharide complex, is given. High- and low-molecular fractions detected by gel filtration technique differed according to the chemical and immunobiological characteristics. The high-molecular fraction of the antigen was found to be highly immunogenic and serologically active.

Animals

A laboratory model for the study of the immunobiology of osteosarcoma.

Inoculation of Moloney sarcoma virus into the marrow cavity of the tibia of newborn Wistar-Lewis rats resulted in the appearance of an initially localized osteosarcoma in 97.7% of these animals. At least 77.9% of the rats developed lung metastases and died, usually within 6 weeks of inoculation. The remaining 22.1% showed regression of disease after initial growth of the tumor. Tumor cells were maintained in tissue culture and used as target cells for a visual and isotopic (3H-thymidine or 125IUdR) microcytotoxicity assay. Cell-mediated immunity could be measured by these methods throughout the course of the illness in animals with progressive disease as well as in those whose tumors eventually regressed. The presence of serum factors capable of modifying the level of CMI was documented. This Moloney-sarcoma-virus-induced rat osteosarcoma and human osteosarcoma thus appear to have several basic pathologic and immunologic similarities. The model may be useful for studying the effects of a variety of treatment protocols upon the clinical course and immune response to osteosarcoma.

Animals