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Biomedical subjects

M Marusić

Publications and source records attributed to M Marusić.

At least 19 recordsLinked to original sources
PubMed1992

New bone induction by demineralized bone matrix in immunosuppressed rats.

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.

Age Factors↗
PubMed1992

Reconstituted basement membrane (Matrigel) promotes the survival and influences the growth of murine tumors.

The effects of reconstituted basement membrane (Matrigel) on in vivo survival and growth of several murine tumors were studied. Survival of tumor cells was enhanced in all experiments which resulted in increased incidence and/or in increased tumor mass. While basement membrane enhanced the in vivo growth of B16F6 melanoma cells, survival of these mice was prolonged. Basement membrane increased the incidence but reduced the growth of Ehrlich ascites tumor. Walker-256 hypercalcemic breast carcinosarcoma growth was enhanced and glandular-like structures were observed when grown on Matrigel. The results indicate that the enhanced survival of tumor cells in the presence of basement membrane is not unequivocally linked with increased malignancy.

Animals↗
PubMed1992

Leukocyte membrane markers on cell populations defined by six flow cytometric bitmaps.

Peripheral blood samples from healthy adults, patients with transplanted bone marrow, and healthy children were analyzed for the proportions of cells positive for CD2, CD4, CD8, CD19, CD56, CDw65, and KiM8 cell membrane markers. Six cell gates were defined on granularity vs. cell size (L90 degrees LSx-FALS) flow cytometric display for each blood sample: large lymphocytic, small lymphocytic, monocytic, mononuclear, granulocytic, and all-cell gate, and the listed markers were determined in each of them. Considerable differences in marker-positive cell proportions were found between healthy adults and children, and particularly between healthy adults and patients with transplanted bone marrow. Marker-positive cell frequencies corresponded to biologic distribution of three leukocyte populations within the defined gates, in a general agreement with known specificities of the antibodies used. A considerable degree of variations in the positions of gates drawn for different samples and the numbers of cells counted in them was observed. Still it appeared that all six gates, otherwise commonly used in flow cytometric analysis, could be precisely defined and yielded reproducible data. large and small lymphocytic gates yielded very similar marker frequencies, revealing that in cases where three leukocyte populations were not clearly delineated on (90 degrees LSxFALS) display, a smaller lymphocytic gate could be safely drawn in order to avoid contamination with monocytes.

Adult↗
PubMed1992

Prognostic significance of cytochemical analysis of leukemic M2 blasts.

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR), i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.

Acid Phosphatase↗
PubMed1992

Humoral immune response to the antigen administered as an immune complex.

Antigen (HSA) bound in immune complexes at equivalence with syngeneic anti-HSA antibodies elicit much stronger humoral immune response then soluble HSA. On the other hand, administration of immune complexes formed with xenogeneic (rabbit) anti-HSA antibodies suppressed humoral immune response against HSA, but not against rabbit IgG in mice. We suggest that immunization with antigen bound in immune complex might represent a powerful tool in enhancing humoral immune responses.

Animals↗
PubMed1992

AgNORs predictive value of prognosis in non-Hodgkin's lymphoma: comparison with flow cytometric cell cycle analysis.

Paraffin-embedded histopathologic specimens, taken before the commencement of therapy from 14 low-grade and 21 high-grade malignant lymphoma patients, and 9 normal lymph nodes were utilized to analyze six cell DNA-related parameters. The flow cytometry technique was used to determine cell-cycle G0/G1, S and G2/M phases, and silver staining to enumerate nuclear organized regions (AgNORs); nucleus surface area was determined by an image-analyzing system. The six parameters and natural logarithm of cell proportion in the S-phase (LS) were determined according to the histologic tumor type and achievement of the first complete remission (CR). All parameters except cell proportion in G1/M cycle phase differed significantly with respect to histologic cell type, but were not related to the achievement of first CR. Inasmuch as the parameters significantly correlated with each other, multivariate discriminant analysis and proportional hazard regression were applied to estimate their discriminant/predictive values with respect to tumor malignancy. AgNORs proved to be far superior in all three clinical parameters, S-phase was significantly predictive for the achievement of first CR, and LS for tumor histology type. The statistical model applied narrowed down the analysis of seven parameters to two with respect to tumor histology type (AgNORs and LS) and achievement of first CR (AgNORs and S), but only to one for overall patient survival (AgNORs). Only the model for tumor histology type discrimination was statistically significant (R2 = 0.904, p < 0.001). It appears that AgNORs may be of utmost predictive importance for the clinical outcome in NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Cellular immune response to the antigen administered as an immune complex in vivo.

Recently, it was shown that 10(2)- to 10(3)-fold lower doses of human serum albumin (HSA) are sufficient for the same T-cell response in vitro, if HSA is administered to the cultures bound in the immune complex rather than in the soluble form. In the present study, we analysed the capacity of HSA in the form of immune complexes to elicit specific cellular immune response in vivo. We found that antigen bound in the immune complex with murine, syngeneic polyclonal antibodies elicited the same T-cell response as fivefold higher doses of free antigen. On the other hand, HSA bound in the immune complexes with xenogeneic, rabbit polyclonal antibodies did not enhance anti-HSA cellular immune response. Our results indicate that binding of antigen in the immune complex could play an important role in enhancing an antigen-specific cellular immune response in vivo.

Animals↗
PubMed1991

Anti-tumoral and anti-inflammatory effects of biological stains.

The biological stains, methylene blue and its metabolite azure B, were evaluated as anti-tumor and anti-inflammatory agents. Azur B, administered in drinking water to tumor-bearing mice, inhibited the growth of transplanted tumors and the growth of primary tumors induced by methylcholanthrene. Inhibition of growth of primary tumors was observed only in female mice. Azure B also reduced the wet weight of carrageenin-induced granulomas in rats. Azure B, given intravenously to BCG-sensitized mice 15 minutes prior to challenge with lipopolysaccharide, decreased TNF production (to 10% of control values) and prevented death from endotoxic shock. Methylene blue decreased TNF production (to 50% of control values) but did not protect the animals from endotoxic shock. Our results suggest that some of the effects previously ascribed to methylene blue are probably mediated via its metabolite, i.e. azure B. Low toxicity and easy administration of the dyes explain their use in clinical settings.

Animals↗
PubMed1991

Modeling autostimulation of growth in multicellular tumor spheroids.

We report the development of a growth model that includes the positive regulatory feedback by cell-cell interactions. It is based on the model by Wheldon et al. (J Theor Biol, 38 (1973) 627) and Cox et al. (Comput Biomed Res, 13 (1980) 445) and is characterized by biologically interpretable parameters. We applied the model to growth of multicellular spheroids formed by V79 Chinese hamster fibroblasts. The new model resulted in a statistically sound fit. We compared the applicability of our model, of the model by Wheldon et al. and Cox et al. as well as of the related model by Piantadosi (Comput Biomed Res, 18 (1985) 220). We affiliated the models with each other within a nesting scheme and compared their respective fits to data by the F-test. Our model yielded a fit statistically equivalent to the fit by the model of Piantadosi. However, in distinction to other models, the estimated cellular doubling time in our model agreed better with the respective experimentally determined value.

Animals↗
PubMed1991

Evolutionary and biological foundations of malignant tumors.

A hypothesis on evolutionary and biological foundations of malignant tumors is developed. It is suggested that malignant transformation is an inevitable facet of the process of senescence, consequent on the accumulation of somatic mutations. The rate of mutation accumulation is determined by an interplay of internal damage to DNA due to metabolic production of oxidative radicals, and effectiveness of DNA-repair mechanisms. The extent of production of oxidative radicals depends on the metabolism intensity which is determined genetically, and is related to the timing of sexual maturation. The timing of sexual maturation depends on the hazard to life of species members--in species exposed to more dangers, reproduction must be set to occur earlier, at the price of having less effective DNA-repair mechanisms. Target genes for malignant transformation are cellular oncogenes. The deaths due to malignant tumors may thus be considered 'one of the mechanisms of death due to aging'. Environmental carcinogens will only modify the incidence of a small fraction of certain tumor types, as other environmental factors modify the death incidence from other causes.

Biological Evolution↗
PubMed1991

Immunological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of nitrous oxide and halothane.

Immunological changes in anaesthetic personnel exposed to occupational concentrations of holothane and nitrous oxide 10-60 times greater than the advised maximum were studied during routine work and after 3-4 weeks holiday. Red cell count, haemoglobin concentration and haematocrit decreased during exposure although not significantly, in comparison with a control group, but all had increased significantly after the holidays. Other changes were altered neutrophils and lymphocyte counts. Basophils disappeared from the blood during the exposure. Monocytes were not affected during the exposure, but increased after its cessation. Percentages of CD2 and CD4 lymphocytes increased significantly, but numbers of cells in T lymphocyte subpopulations (total, helper and cytotoxic/suppressor lymphocytes) were not significantly altered. B lymphocytes were most strongly affected: they decreased during working periods and did not recover after holidays. Natural killer (NK) cells, on the other hand, decreased significantly during exposure, but fully recovered during holidays. After stimulation with mitogens, phytohaemaglutin, concanavalin A, and pokeweed, lymphocytes from exposed personnel incorporated significantly more 3H-thymidine than those from control subjects, but stimulation indices did not differ. The natural killer-cell activity, serum Ig concentrations and phagocytosis by granulocytes were not altered.

Adult↗
PubMed1991

T cell subset composition in remission phase of systemic connective tissue diseases.

The proportions and numbers of peripheral blood mononuclear cells bearing T-cell markers (CD3/HLA-DR, CD4/CD29, CD4/CD45, CD8/CD56) were analyzed using two-color flow cytometric analysis in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) in the remission phase of the diseases. The number of T cells (CD3+) in the blood was significantly decreased in SLE patients only; in these patients, but also in RA patients, an increased number of activated T cells (CD3+ HLA-DR+) was found. The number and proportion of helper T cells (CD4+) were decreased in SLE and SS, and normal in RA patients. In contrast, helper-inducer (CD4+ CD29+) and suppression-inducer (CD4+ CD45+) cells were both significantly increased in RA patients, decreased in SLE (only CD4+ CD45+ significantly) and unchanged in SS patients. Interestingly, however, the proportions of helper-inducer cells relative to total helper (CD4+) cell pool were significantly increased in all three groups of patients, whereas the proportion of suppression-inducer (CD4+ CD45+) cells was significantly decreased, but in SLE patients only. It is thus possible that this parameter is most pertinent to the disease status in the model studied. The population of CD8+ cells appeared more abundant in SLE patients, and the pool of CD8+ CD56+ cell was significantly enlarged in RA patients. It appears that the remission phase of disease in RA, SLE and SS patients still contains a substantial activation of the immune system, but the respective mechanisms are quite different in RA patients on one side, and SLE and SS patients on the other side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Natural killer cell number and activity in remission phase of systemic connective tissue diseases.

The proportions and numbers of peripheral blood mononuclear cell markers and peripheral blood NK cell activity were analyzed and correlated in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) patients in the remission phase of the diseases. In comparison to the control data, the number of CD56+ cells was significantly increased in RA patients only; the same held true for double-positive cells, i.e., the alterations did not distinguish various subpopulations of NK cells. NK cell activity was significantly decreased in all the three groups of patients, with the complete lack of correlation between the NK cell number and their activity. It is possible that a significantly diminished NK cell activity in these diseases provokes a compensatory production of nonfunctional NK cells.

Adult↗
PubMed1990

Immunological aspects of progeria (Hutchinson-Gilford syndrome) in a 15-month-old child.

A thorough analysis of the immunological status was conducted in a 15-month-old child with progeria (Hutchinson-Gilford syndrome). Total leukocyte and neutrophil counts were slightly increased, and monocytes were decreased. Percentage and numbers of CD4+ cells in the blood were mildly decreased as well as the CD4/CD8 cell ratio. CD20 (B-cell marker) bearing cells and cells bearing Ia-antigens were increased, as well as CD16 and CD56 marker-bearing cells (natural-killer cells, NK). Lymphocyte proliferation upon stimulation with phytohaemagglutinin and purified protein derivative were decreased, and with pokeweed mitogen increased. NK cell activity appeared increased, particularly at lower effector: target cell ratios.

Agammaglobulinemia↗
PubMed1990

Cellular and morphological changes in lymphoid organs after a single injection of interleukin 1 alpha in the mouse.

We investigated the effects of a single i.v. injection of recombinant human interleukin 1 alpha (IL-1 alpha) on the morphology and the cellularity of several lymphoid organs in normal mice. The injection of 100 U of IL-1 alpha resulted in maximal neutrophilia and leukocytosis at 1 h. By 72 h, the numbers of mononuclears, but not that of polymorphonuclears, returned to baseline levels. Absolute increase in mononuclears was paralleled by relative lymphopenia. Changes in the peripheral blood coincided with rapid decrease in the spleen cellularity and white pulp volume (especially the marginal zone), and an increase in the red pulp volume. Bone marrow cellularity was increased at 1 h, but returned to control levels by 6 h after IL-1 injection. Thymus cell depletion and cortex atrophy were maximal at 6 h and could be observed throughout the experiment. These findings indicate that leukocytosis induced by a single i.v. injection of IL-1 alpha in normal mice is concomitant with a rapid cell depletion of the spleen and thymus. Morphological and cellular changes in lymphoid organs may represent the mobilization of immunocompetent cells during the development of the inflammatory response.

Animals↗
PubMed1990

Relationship between differing volumes of bone marrow aspirates and their cellular composition.

We compared the cellular composition of the first 1.0 ml volume bone marrow aspirate with that of an aliquot from the total bone marrow harvest at the end of the procedure in 17 healthy bone marrow donors. Each sample was assayed for its content of red blood cells, nucleated cells, CD2+, CD4+, CD8+, CD19+, HLA-DR+, CD56+, CD13+, CD33+, CD34+ and KiM8+ cells and CFU-GM. On the basis of data obtained, we estimated that the first 1.0 ml samples had 8.0 +/- 5.2% (SD) and the transplant samples 20.8 +/- 8.5% contamination with nucleated blood cells. The calculation revealed that both types of bone marrow samples had 100% volume contamination with peripheral blood, i.e. that bone marrow cells were aspirated within blood fluid volume. Nucleated cell concentration was 3-fold, and CFU-GM concentration 10-fold lower in the transplant than in the first-puncture 1.0 ml bone marrow samples. Various marker-positive cells appeared in transplant samples in concentrations that depended on their abundance in the first-puncture 1.0 ml and blood samples. Taken together, our data suggest that bone marrow harvesting would be substantially improved if individual aspirates were small in volume and taken from bone puncture sites as distant as possible.

Adolescent↗
PubMed1990

Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia.

From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%).

Adolescent↗