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Biomedical subjects

F Garrido

Publications and source records attributed to F Garrido.

At least 181 records · Page 10Linked to original sources

Syngeneic tumor cells can induce alloreactive T killer cells: a biological role for transplantation antigens.

A chemically induced sarcoma of BALB/c (H-2d) mice, MCG4, is shown to induce in BALB/c lymphocytes a primary anti-tumor cytolytic T lymphocyte (CTL) reaction in vitro. The anti-tumor CTL showed tumor specificity but reacted also with normal cells expressing distinct H-2 alloantigens. The CTL response could be shown to be induced by and directed against alloantigenic determinants expressed on two different molecules, one H-2Kk-like the other H-2Dk-like. The biological significance of these findings is discussed with regard to (i) possibility of derepression of normally silent H-2 genes in tumor cells and normal cells, (ii) generation of alloreactivity in ontogeny, and (iii) role of alloreactive T cells in eliminating cells expressing wrong gH-2 antigens.

Animals↗

Expression of foreign H-2-like antigens by a chemically-induced murine tumour (MCG4).

Alien H-2k-like antigens were found to be expressed by a methylcholanthrene induced tumour of BALB/c (H-2d) origin. H-2 specificities of the k haplotype were detected on this tumour by a variety of serological techniques, including 51Cr-release cytotoxicity, microradioassay and absorption. The antisera employed were conventional polyspecific alloantisera, typing sera with restricted specificty and monoclonal hybridoma-derived anti-H-2k antibodies. The tumour has a low expression of the private specificty 31, which characterizes Kd molecules, and does not seem to express the private specificities of Dd, Kk and Dk molecules. It appears to express predominantly alien H-2-like antigens which are very similar to but not identical with normal H-2k molecules.

Animals↗

Hormonal control of RNA polymerases in rat bone marrow nuclei. The action of erythropoietin and testosterone.

The cytodifferentiation of stem cells to mature cells in bone marrow is an appropiate system to study biochemical aspects of hormonal action. We have used this system to analyze the way how erythropoietin and testosterone regulate erythropoiesis at the molecular level. Experiments designed to correlate the biochemical action of both hormones and to determine their differential action on rat bone marrow nuclei DNA-dependent RNA polymerases are reported. The effect of both hormones on the synthesis of RNA by isolated nuclei derived from normal rats was studied. Erythropoietin enhances the activity of RNA polymerase type II while testosterone stimulates polymerase type I activity. Gel-electrophoresis analysis of nuclear RNA shows that erythropoietin enhances the synthesis of RNA species with sedimentation coefficients of 30S, 22S, 15S, and 9S. Testosterone stimulates the synthesis of the 28 and 18S RNA as well as 4S RNA. A model is postulated to explain the action of erythropoietin and testosterone on RNA synthesis by isolated rat bone marrow nuclei.

Animals↗

A comparative study between Fc receptor bearing cells and antibody dependent cell cytotoxicity in cancer patients.

The capacity of 14 cancer patients lymphoid cells to destroy antibody-coated target cells (antibody-dependent cell cytotoxicity ADCC), and to form rosettes with immunoglobulin-coated erythrocytes (EA) was compared. The lymphocyte functions were investigated immediately prior to chemo-immunotherapy. Our observations show a correlation between the percentage of EA-rosette forming cells and ADCC activity of cancer patients and controls. However, the regressive lines were different in both groups. Interestingly, cancer patients with a lower. EA rosette forming cells than controls, showed higher cytotoxic activity.

Adult↗

Absence of four H-2d antigenic specificites in an H-2d sarcoma.

MCG4 is a BALB/c sarcoma induced as a solid tumour with 0.2 mgs of methylcholantrene. The primary tumour was serially transplanted subcutaneously in syngeneic mice. The ascites form obtained was sued to study the expression of H-2 antigeneic specificities in a postlabelling radioassay. MCG4 did not express H-2D.4 (private specificity of H-2d haplotypes) as well as H-2.3, H-2.8 and H-2.13 (public specificities). In addition it expressed H-2.5 (a public specificity not present in H-2d cells). These results were confirmed by quantitative absorption analysis using MCG4 and positive-negative normal lymphoid cells for a particular specificity. Results are discussed with regard to the control of expression of H-2 antigens by regulatory genes.

Animals↗

[Strain-specific antigens detected on murine tumour cells by means of rabbit heteroantisera (author's transl)].

The rabbit heteroantisera anti-Meth A sarcoma (H-2d) (RAMA) and rabbit anti-RBL-5 leukemia (H-2b) (RAR-5) have been used to study the presence of normal strain antigens on the surface of different murine tumour cells. RAR-5 detected H-2-like structures on TLX9 (H-bb) lymphoma, however RAMA did not on LSTRA leukemia (H-2d) mastocytoma. Neither RAR-5 nor RAMA contained antibodies against non-H-2 and differentiation antigens.

Animals↗

A syngeneic anti tumor serum recognizing a complex H-2 alloantigen.

A methylcholanthrene induced tumor of BALBc (H-2d) origin had a high rate of spontaneous regression when transplanted into syngeneic animals. The tumor induced in BALB/c mice iso-antibodies with high anti-tumor cytotoxic activity. A specificity analysis of such BALB/c anti MCG4 sera revealed that the antibodies were directed against a tumor antigen which is very similar to H-2- alloantigens (e.g. H-2.5) expressed on normal cells of certain foreign mouse strains. The sera also reacted with nine out of ten B10.W congenic strains bearing H-2wi haplotypes derived from wild mice. Whether the tumor antigen is identical with foreign H-2 antigens or only cross-reactive cannot be decided at present.

Animals↗

Hormonal control of gene expression: differential activation of rat bone marrow RNA polymerases by erythropoietin and testosterone.

Hormones play a role in the regulation of gene expression by inducing changes in enzyme patterns in target cells mediated by the synthesis of specific RNA molecules. Erythropoiesis has been used as a system for studying the molecular mechanism of regulation of gene action by means of two hormones: erythropoietin and testosterone. Experiments designed to correlate the biochemical action of both hormones on rat marrow cells are herein reported. Both factors seems to act at different biochemical and citological levels. Erythropoietin triggers the erythropoietic process acting on the erythropoietin sensitive cells (ESC), in which the hormone induces the synthesis of a high molecular weight RNA, which is the precursor of a functional 9 S messenger RNA. Testosterone seems to act on polychromatophilic erythroblasts, in which the synthesis of ribosomal RNA or its precursor is stimulated. The steroid enhances the nuclear ribonuclease activity, which could represent a control mechanism for the processing (maturation) of high molecular weight RNAs. The incorporation of 3H-GTP and 3H-UTP into RNA by isolated rat bone marrow nuclei is stimulated by erythropoietin and testosterone. Using alpha-amanitine and different ionic strength conditions it was found that erythropoietin enhances preferentially RNA polymerase II activity while testosterone increases RNA polymerase I activity. It is postulated that erythropoietin and testosterone act synergically to create the biochemical machinery for hemoglobin synthesis, the macromolecule that characterizes the erythropoietic process.

Amanitins↗

H-2 typing of RBL-5, TLX/9 tumour cells and L929 fibroblast.

The H-2 specificities in two different H-2b tumour cells (TLX/9 and RBL-5) and a fibroblast line L929 (H-2k) have been studied. Tumour cells were passaged intraperitoneally in syngeneic mice and fibroblast was kept in vitro at 36 degrees C. The typing was performed by means of a postlabelling microradioassay for actively growing cells and 28 H-2 alloantisera of restricted specificity defining private H-2K, H-2D and public antigens. Unexpected reactions in disagreement with H-2 genetics were detected in both tumours but not in fibroblast line. The latter shed C-type particles whereas RBL-5 did not. The cytotoxicity of the alloantisera was quantitatively absorbed by normal lymphoid cells, although some extrareactivities were due to other antibodies present in the sera. RBL-5 grew in mice of different H-2 haplotypes with the same intensity as in syngeneic animals.

Animals↗

Emergence of foreign H-2-like cytotoxicity and transplantation targets on vaccinia and Moloney virus-infected Meth. A tumour cells.

Using cytotoxic effector cells of different anti-H-2 specificities, new cell-mediated lympholysis targets, normally undetected on Meth. A tumour cells, were shown after passage with vaccinia or Moloney virus. The H-2d CML targets on Meth. A cells recognized by B10.BR anti-B10.D2 effector cells were presented only after simultaneous vaccinia virus passage, while passage with Moloney virus caused the emergence of H-2b targets. Small but significant killing of vaccinia virus-passaged Meth.A was also obtained by anti-H-2k effector cells. These results are discussed in relation to in vivo experiments: retardation of tumour growth was noted in mice which had received several injections of vaccinia or Moloney virus, showing that the new CML targets were probably acting as transplantation targets.

Animals↗

Studies on H-2 specificities on mouse tumour cells by a new microradioassay.

Seven mouse tumour cell lines of different aetiology and origin were tested for the expression of surface alloantigens using twenty-four well defined H-2 alloantisera and anti-Thy 1.2. We used a new radioassay that involves antibody-complement treatment of the tumour target cells followed by postlabeling the surviving tumour cells with 14C-thymidine. With a relatively high frequency the anti-H-2 sera were reacting differently with the tumour cells than with respective syngeneic lymphoid cells. Thirty-six anomalous reactions out of 129 investigated were detected. Absorbtion experiments performed with H-2 antigen positive or negative lymphoid cells revealed a striking similarity between these extra-specificities and H-2 specificities of foreign haplotypes. The results are discussed in relation to the biological importance of the extra-specificities, both with regard to origin (derepression) and function (transplantation antigen properties).

Animals↗

Studies on T cells in newborns. Higher reactivity of umbilical cord blood lymphocytes to PHA as measured by whole blood microtechnique.

The capacity of human foetal lymphocytes to respond to PHA and to form E-rosettes have been compared with data from adult individuals. For this purpose a microculture system that uses whole blood and avoids the problems of lymphocyte separation, has been developed. Foetal lymphocytes reached optimal stimulation with lower dosis of PHA (31,2 microgram/ml) as compared with adult cells (125-252 microgram/ml). However their quantitative response (measured by 14C-thymidine uptake) was equal in both groups. In addition, peripheral T cells (E-rosetting cells) reached values of 36.47 +/- 9% in newborn and 49.6 +/- 10% in normal adult controls. These results are discussed as to the status and development of cellular inmunity in human foetus.

Adult↗