Biomedical subjects
Publications and source records attributed to E Moldoveanu.
BCL-2 protein is a oncoprotein considered to have an important role in the regulation of programmed cell death--apoptosis. The intracellular localization, the relation with other oncoproteins, the antioxidant function and the pathological implications are discussed.
Free radicals that appear during physiological processes may lead to apoptosis in some pathological conditions when antioxidant capacity of the tissue is surpassed. Additionally, free radicals are involved in the control of apoptosis; antioxidant agents suppress apoptosis induced by a variety of stimuli. The possibility that apoptosis is regulated by modulation of the levels of free radicals is discussed.
One case of T-cell lymphoma with atypical malignant cells is reported. Some of the clinical features, morphological characteristics and functional activity (erythrophagocytosis) of malignant cells suggested malignant histiocytosis. The malignant disease started with splenomegaly and developed with hepatomegaly, bone marrow infiltration, discrete lymphadenopathy and leukaemic picture. Proliferated cells were characterized by ambiguity. In addition to phagocytic capability, presence of complement receptors and ultrastructural features proper to the macrophagic lineage, the cells expressed T-cell determinants (E receptors, T3, T4 and T11 antigens) and were peroxidase and esterase-negative. Erythrocytes were partially or completely dehaemoglobinized and presented the phenomenon of autolysis in different stages of development. Because this lymphoma is difficult to diagnose and apparently resistant to therapy, its recognition and further study are warranted.
A patient with non-cutaneous lymphocytic lymphoma with leukaemic spread is reported. The large majority of the peripheral blood mononuclear cells formed rosettes with sheep erythrocytes (E), had receptors for the Fc portion of IgG (Fc gamma R) and displayed an unusual enzymatic profile. Part of these cells had also labile bound surface membrane IgG. The leukaemic cells were morphologically characterized as large granular lymphocytes (LGL) and consisted of two different types of cells: lymphoid cells and monocytoid cells. The histopathological diagnosis was T-cell lymphoma, pleomorphic type, diffuse. Despite their morphological heterogeneity, all the proliferative cells had the same immunological phenotype, showed normal ADCC activity but no NK activity. After three months, without specific treatment, the surface pattern changed: the cells resembled mature LGL and the NK activity increased. The cytochemical study of the leukaemic cells revealed an enzymatical peculiarity: besides an enzymatic profile characteristic for relatively mature LGL, the cells also displayed peroxidase activity. This unusual aspect--the expression by an individual malignant cell of markers believed to be restricted to a single cellular lineage--might be interpreted as a lineage infidelity or lineage promiscuity. The observation that this lymphoma developed in a patient with a long history of hypogammaglobulinaemia is of particular interest.
Multivalent hybrid antibody (MHA) complexes with dual specificity were prepared by combining two antibodies of different specificities, one against ferritin (Fer), the other against horseradish peroxidase (HRP), with protein A of Staphylococcus aureus (SpA). Electron microscopy of mouse spleen lymphocytes and thymocytes (previously coated with mouse IgG anti-Thy-1 antibody) treated with IgG anti-Fer/SpA/IgG anti-mouse Ig complex and Fer gave better resolution and higher accuracy than previously obtained with IgG anti-HRP/SpA/IgG anti-mouse Ig complex and HRP (Mandache et al., 1980). Surface Thy-1 alloantigen and Fc receptor (charged with human IgG) treated with a mixture of IgG anti-Fer/SpA/IgG anti-Thy-1 and IgG anti-HRP/SpA/IgG anti-human Fab could be simultaneously detected on the thymocyte surface by either light or electron microscopy using Fer and HRP. The concomitant visualization of Thy-1 alloantigen (with Fer) and FcR (with HRP) on mouse thymocyte clearly shows that their distribution is largely independent and that the amount of Thy-1 antigen is greater. These results show that electron microscopy with a mixture of MHA is a useful technique for simultaneous location of two antigenic markers on the cell surface.
Multivalent hybrid antibody complexes with dual specificity were prepared by combining rabbit antibody with anti-mouse immunoglobulin (mIg) and anti-peroxidase (HRP) specificity using protein A of Staphylococcus aureus. The presence of two antibody molecules with anti-mIg and anti-HRP specificity in a single molecule of hybrid complex was demonstrated by their abilities to produce hemagglutination with both HRP-coated and mIg-coated sheep red cells, to give a reaction of complete identity with mIg and HRP and to allow mIg bearing lymphocytes to form rosettes with HRP-coated sheep red blood cells. Electron microscopy of mouse lymphocytes and thymocytes (previously coated with mIg anti-Thy-1 antibody) treated with hybrid antibody complex and HRP showed strong and specific staining of the cell membrane of both cell types. The hybrid antibody complex containing anti-HRP antibody is a valuable reagent for determining various antigenic markers on cell membranes by electron microscopy.
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This paper is part of a series aimed to investigate the mechanism of the action of Folcysteine, a substance that has the capacity to release in the body active -SH groups and has been proved to be effective in the control of menopausal troubles. As an experimental model the ovariectomized rat, rather similar, from the viewpoint of the hormonal balance, to the aged female, has been considered. Under these conditions, the effect, at the uterine and adrenalian level of the treatment with two different doses of estradiol with Folcysteine alone as well as associated with estradiol, has been investigated. Our results indicate that the active -SH groups released by Folcysteine intensify the effect of estrogens upon the uterine tissue and stimulate the estrogen biosynthesis at adrenalian level.
The Kupffer cells, as fixed macrophages, belong to the mononuclear phagocyte system (MPS), the former reticulo-endothelial system (RES). Their ultrastructure has some characteristics, i.e. ergastroplasmic peroxidase activity and worm-like structures, which allow a very sharp identification. Some particular "bridge-like" arrangements of Kupffer cells in the capillary lumen seem to provide them with a special ability of "trapping" the passing white blood cells. The important endocytotic function is analysed from the viewpoint of ultrastructural features, and with particular reference to the phagocytosis of damaged red blood cells. Several drugs and particulate substances acting as Kupffer cells stimulants are presented. This stimulation reaction concerns woth increased number and enhanced endocytotic activity. The origin and kinetics of Kupffer cells are discussed, with reference to own results which substantiate the theory of local proliferation and blood supply, the bone marrow being however the main source of hepatic macrophages. A few ultrastructural data on Kupffer cells involved in pathological processes are presented.
Electron microscopic investigation allowed the identification and characterization of the atypical malignant cells in a case of T-cell lymphoma. The proliferating cells were endowed with characteristics belonging to two different lineages: phagocytic ability, complement receptors and ultrastructural features proper to the macrophagic lineage, and T-cell determinants (E receptors, T3, T4 and T11 antigens). The cells were peroxidase and esterase negative. The erythrocytes were partially or completely dehemoglobinized and presented the phenomenon of autolysis in different stages of evolution. Because this lymphoma is difficult to diagnose and is apparently resistant to therapy, its recognition and further study are warranted.
The investigation has been carried out on stimulated and unstimulated peritoneal cavities of rats. China ink and Corynebacterium parvum were injected i.p. both as peritoneal stimuli and markers. Omenta were picked up at time intervals beginning with 10 min and up to seven days after the i.p. injection. The light and electronmicroscopic investigation showed after 10-30 minutes labeled macrophages stuck as monolayers on some peritoneal areas corresponding to the milky spots which developed in size and number. Days after the i.p. injection the labeled macrophages were found deeper in the milky spots. After the fourth day they appeared in the regional lymph nodes. The milky spots contained also large lymphocytes and plasma cells. The results suggest that milky spots are not only places of resident macrophages development and release in the peritoneal cavity but also their exit pathways. Therefore the omentum leads the traffic of peritoneal macrophages. The developed milky spots play also the role of lymphoid structures providing grounds for macrophage-lymphocyte contacts.
A case of acute leukemia with atypical malignant cells is reported. The clinical picture and coagulation studies were consistent with a disseminated intravascular coagulation syndrome. Morphologically, the leukemic cells from the peripheral blood and bone marrow showed azurophilic granules. More than 80% of cells were hypergranulated, resembling the macrogranular type of promyelocytes. Ultrastructural studies and the pattern of endogenous peroxidase were consistent with the microgranular type of promyelocytes in about 20% of the leukemic cells. Auer bodies were present in both types of atypical promyelocytes. Cytochemically, the whole malignant population exhibited intense peroxidase activity. Studies with monoclonal antibodies showed that about 45% of the proliferating cells expressed T-cell markers T3, T4, T8 and T11, but the cells were not reactive with OKM1 monoclonal antibodies. The chemotherapy for acute promyelocytic leukemia was inefficient, and the prompt disappearance of the blood abnormalities was observed only when chemotherapy for acute lymphoblastic leukemia was started. Therefore, it seems that in some cases of leukemia with hybrid types of malignant cells the morphological features determine the clinical picture, while the patient's response to the therapy is conditioned mainly by the cell surface phenotype.
China ink and typhoid vaccine were used as peritoneal stimuli injected in single doses. The subsequent omental reaction was studied after several time intervals: 6 and 12 hours, 1, 2, 3, 4 and 8 days, 3 and 6 weeks. The omental reaction featured as lymphatic nodules connected to milky spots was compared with a primary immune response. The ultrastructure and development of the characteristic cells (lymphocytes, lymphoblasts, dendritic reticulum cells, tingible body macrophages and plasma cells) was investigated throughout the period from 6 h to 6 weeks. A special attention was devoted to ultrastructural and functional features of plasma cells.
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