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M Marusić

Publications and source records attributed to M Marusić.

At least 19 recordsLinked to original sources
PubMed1996

Prognostic parameters for survival of patients with malignant mesenchymal tumors of the uterus.

BACKGROUND: Malignant mesenchymal uterine neoplasms are the most aggressive type of primary uterine tumors, with most patients dying within a few years of diagnosis. Thus, it would be very important to define prognostic factors for predicting the malignancy potential of at least some of their subtypes. METHODS: Flow cytometric cell cycle analysis (proliferative activity, DNA ploidy, and DNA index) was performed on archival paraffin embedded blocks from 80 patients with malignant mesenchymal uterine neoplasms (endometrial stromal sarcomas, malignant smooth muscle tumors, and malignant Müllerian mixed tumors). The Cox proportional hazards regression model was used to assess relative effects of the following factors on patient survival: clinical stage, mode of therapy, DNA+proliferative activity, DNA index, histologic type, cellularity, degree of atypia, mitotic activity, and depth of myometrial invasion. RESULTS: There were 9 low grade stromal sarcomas, 17 high grade stromal sarcomas, 8 smooth muscle neoplasms with uncertain malignant potential, 23 leiomyosarcomas, and 16 homologous and 7 heterologous malignant Müllerian mixed tumors. In univariate analysis for stromal sarcomas, statistical significance was found for DNA ploidy+proliferative activity (P < 0.001), histologic type (P = 0.005), and DNA index (P < 0.001). In multivariate analysis, DNA index appeared to be the only significant parameter influencing patient survival (P = 0.005). In univariate analysis for malignant smooth muscle neoplasms, statistical significance was detected for mitotic activity (P = 0.049) and International Federation of Gynecology and Obstetrics classification (P = 0.021), but in multivariate analysis, clinical stage appeared to be the only significant parameter influencing patient survival (P = 0.032). In univariate analysis for malignant Müllerian mixed tumors, statistical significance was found for the depth of myometrial invasion (P = 0.039), DNA index (P = 0.037), and clinical stage (P = 0.013), but in multivariate analysis, only the depth of myometrial invasion (P = 0.036) and clinical stage (P = 0.025) were of statistical significance. CONCLUSIONS: The most powerful prognostic indicator for stromal sarcomas was the DNA index, for malignant smooth muscle neoplasms it was the clinical stage, and for malignant Müllerian mixed tumors it was the depth of myometrial invasion.

Analysis of Variance↗
PubMed1996

Binding of anti-double stranded (ds) DNA-positive sera to denatured (d) DNA and synthetic poly[dA-dT] x poly[dA-dT] double stranded copolymer in an ELISA format.

Using an ELISA assay anti-nuclear antibody-positive sera from 300 patients with various immune-related diseases and 64 anti-nuclear antibody-negative sera were analysed for binding to S1-nuclease-treated double stranded (ds) DNA. In addition, the pattern of reactivity of 50 selected anti-dsDNA-positive sera was established using denatured (d) DNA and poly[dA-dT] X poly[dA-dT] double-stranded alternating copolymer (dAT) as additional DNA antigens. None of the 64 anti-nuclear antibody-negative sera and 76 of the 300 anti-nuclear antibody-positive sera (25%) were anti-dsDNA-positive. Of the anti-nuclear antibody-positive and anti-dsDNA-positive sera, 48 (63%) were from systemic lupus erythematosus patients, and 7 (9%) from rheumatoid arthritis patients, whereas 21 patients (27.6%) suffered from various immune and non-immune related diseases. Anti-dsDNA-positive reactivity was highly correlated with dDNA and dAT reactivity (r = 0.906, p < 0.0001 and r = 0.93, p < 0.0001, respectively). Although the majority of the 50 selected (37 systemic lupus erythematosus and 13 non-systemic lupus erythematosus) anti-dsDNA-positive sera concomitantly bound to both additional antigens, 7 of these (14%) did not bind to dAT, and 2 (4%) did not bind to dDNA. Anti-dsDNA-positive sera (n = 37) showed a similar pattern, in which 8.1% and 2.7% of sera did not bind to dAT and to dDNA, respectively. In contrast, anti-dsDNA-negative sera from various immune-related diseases bound either ssDNA (12.5%) or dDNA and dAT (12.5%). These data suggest that dsDNA and dAT-based assays detect similar but not identical specificities in the sera of patients suffering from systemic lupus erythematosus and in a proportion of non-systemic lupus erythematosus patients.

Antibodies, Antinuclear↗
PubMed1995

Phorbol 12-myristate 13-acetate-mediated signalling in murine bone marrow cells.

Phorbol 12-myristate 13-acetate (PMA)-mediated signalling was investigated in relation to the ability of murine (CBA) bone marrow cells to form colonies in vitro. Treatment of marrow cells with PMA did not influence the 1,2-diacylglycerol or cyclic AMP concentrations, the intracellular Ca2+ concentration or phospholipase D activity. PMA increased particulate phospholipase A2 (PLA2) activity, lysophosphatidylcholine formation and arachidonic acid release from bone marrow cells; these effects were abolished when cells were pretreated with the putative PLA2 inhibitors heparin and mepacrine. While indomethacin and nordihydroguaiaretic acid inhibited either the cyclo-oxygenase or lipoxygenase pathway of arachidonic acid metabolism, as measured by their products prostaglandin E2 and leukotriene B4, they did not influence PMA-mediated PLA2 activation or translocation of protein kinase C (PKC) from the soluble to the particulate fraction. Treatment of cells with PMA increased the amounts of membrane-bound alpha, beta, delta, epsilon and zeta isoforms of PKC in bone marrow cells. Pretreatment of cells with PLA2 inhibitors reduced the amount of membrane-bound PKC-zeta in unstimulated cells and diminished PMA-induced translocation of PKC-zeta to membranes without affecting other PKC isoforms. This effect could be overcome by exogenous addition of arachidonic acid, suggesting that PKC-zeta may operate downstream of the activated PLA2. On the other hand, wortmannin, an inhibitor of phosphatidylinositol 3-kinase, did not influence the amount of PKC-zeta associated with particulate fractions in control cells and could not abolish the PMA-mediated translocation of this isoform. Short-term exposure (45 min) of bone marrow cells to PMA, phorbol 12,13-dibutyrate or arachidonic acid increased the number of colonies formed over 7 days in a methylcellulose-based culture in vitro. The effects of PMA, but not those of arachidonic acid, could be prevented by putative PLA2 inhibitors. This suggests that PMA-mediated activation of conventional PKCs and novel PKCs leads to PLA2 activation which, by releasing arachidonic acid from phospholipids, activates PKC-zeta. This signalling pathway appears to be mitogenic for bone marrow cells.

Animals↗
PubMed1995

Significance of aneuploidy in non-Hodgkin lymphomas.

The incidence of aneuploidy was determined by flow cytometric analysis in paraffin-embedded tumor samples of 125 patients with non-Hodgkin lymphoma (NHL). There were 48 low-grade (LG) and 77 high-grade (HG) tumors. Aneuploidy was found in 34 (27%) NHL, 15 (31%) LG, and 19 (25%) HG tumors. The analysis of patient survival showed a significantly better survival of patients with LG than HG NHL, but the presence of aneuploidy did not influence the survival on the level of all patients, patients with LG or patients with HG NHL. In patients with LG NHL a tendency of diploid vs. aneuploid patients to survive longer was observed, but only at P = 0.056 significance level.

Aneuploidy↗
PubMed1995

Short-term and long-term-effects of phorbol 12-myristate 13-acetate and different inhibitors on the ability of bone marrow cells to form colonies in vitro.

The process of signal transduction responsible for the phorbol 12-myristate 13-acetate mediated increase in the colony-forming potential of murine (CBA) bone marrow cells was studied using known modulators of the mitogenic signal. Pretreatment of cells for 60 minutes with staurosporine (1 mumol/l), an inhibitor of protein kinase C, completely prevented colony formation in the control group of cells and significantly reduced the number of colonies formed in the phorbol ester-treated group. Brief exposure (60 min) of cells to the phospholipase A2 inhibitors, mepacrine (500 mumol/l) and heparin (1 g/l), reduced the number of colonies formed in the control group and completely abolished the increase in the number of colonies formed after treatment of the cells with phorbol ester. When inhibitors of protein kinase C or phospholipase A2 were present during the entire period of the colony forming assay (7 days), no colonies could be scored in either the control or phorbol ester-treated groups of bone marrow cells. Long-term treatment or temporary exposure (60 min) of cells to indomethacin (50 mumol/l), an inhibitor of cyclooxygenase, or nordihydroguaiaretic acid (50 mumol/l), an inhibitor of lipoxygenase, had no effect on colony formation in both groups. Pretreatment of cells for 45 min with calcium ionophore A23187 (10 mumol/l) failed to increase the number of colonies, compared with the control group. Moreover, simultaneous treatment of cells for 45 min with phorbol ester (500 nmol/l) and A23187 (10 mumol) did not produce any further increase in the number of colonies, compared with the phorbol ester-treated group, suggesting that elevation of intracellular calcium is unimportant in the phorbol ester-mediated response. Dibutyryl cyclic adenosine monophosphate (50 mumol/l) in the presence or absence of phorbol ester, failed to stimulate colony formation, indicating that cyclic AMP-dependent protein kinases are not involved in the signalling process. Temporary exposure (75 min) of bone marrow cells to okadaic acid (1 mumol/l), a potent inhibitor of serine/threonine phosphatases, or to tyrphostine AG-115 (20 mumol/l), a tyrosine kinase inhibitor, did not effect colony growth in the control or phorbol ester-treated group. The results indicate that phospholipase A2 activation is involved in the phorbol ester-mediated increase in colony formation, since, of the different agents applied, only staurosporine, an inhibitor of protein kinase C, and mepacrine and heparin, putative inhibitors of phospholipase A2, were capable of abolishing phorbol ester-mediated effects.

Animals↗
PubMed1995

Granulocyte-monocyte colony forming unit content of autologous bone marrow transplants in patients with haematological malignancy.

Cell viability and number of granulocyte-monocyte colony forming units (CFU-GM) were systematically assessed in 57 patients who had undergone transplantation of the autologous bone marrow for treatment of haematologic malignancies. Bone marrow cell cultivation in agarose with feeder layers appeared inferior to that performed in agarose with recombinant human granulocyte-monocyte colony stimulating factor and methylcellulose with phytohaemaglutinin leukocyte-conditioned medium. Since the transplant cells were frozen in liquid nitrogen between harvesting and reinfusion, the following samples were tested: buffy coat cells, buffy coat cells immediately after addition of dimethylsulphoxide, cell sample that had been frozen for 24 hours, and frozen transplant cells at the time of thawing and transplantation. Each procedural step decreased both cell viability and the number of CFU-GM, but since the lymphohaematologic recovery in all patients followed the pattern reported in the literature for high-quality transplants, we concluded that our transplants retained the necessary number of progenitor cells. It appears that the best strategy for dynamic assessment of the transplant quality would be to perform tests after every step of the transplant processing. Cell viability and number of progenitors per body weight in transplants were also found to be associated with probability of neutrophil reconstitution after bone marrow reinfusion.

Adolescent↗
PubMed1994

Tumor cell cycle in patients with stage I endometrial carcinoma.

Flow cytometric cell cycle analysis was performed on paraffin-embedded blocks from 49 patients with stage I endometrial carcinoma. Care was taken to separate tumor tissue from normal tissue in each specimen; normal tissue was used as a control for each individual specimen. DNA index, proliferative activity, and cell DNA aneuploidy were correlated with known parameters of tumor malignancy. Increased DNA index corresponded well with the DNA aneuploid tumors, poor tumor differentiation (G3), myometrial invasion of more than one-third, more malignant histologic type of tumor, and low concentration of estrogen (< or = 10 fmole/mg) and progesterone (< or = 25 fmole/mg) receptors. Similar results were obtained for tumor cell proliferative activity (percentage of cells in S + G2/M phases) and for DNA aneuploid tumors. Since more than 90% of patients with stage I endometrial carcinoma survived the 5-year postoperation period, analyzed parameters could not be checked for survival-related prognostic significance. However, our data indicate that cell cycle analysis may be instrumental for objective ranking of several known prognostic parameters.

Adult↗
PubMed1994

Tumor growth in vivo and as multicellular spheroids compared by mathematical models.

In vivo volume growth of two murine tumor cell lines was compared by mathematical modeling to their volume growth as multicellular spheroids. Fourteen deterministic mathematical models were studied. For one cell line, spheroid growth could be described by a model simpler than needed for description of growth in vivo. A model that explicitly included the stimulatory role for cell-cell interactions in regulation of growth was always superior to a model that did not include such a role. The von Bertalanffy model and the logistic model could not fit the data; this result contradicted some previous literature and was found to depend on the applied least squares fitting method. By the use of a particularly designed mathematical method, qualitative differences were discriminated from quantitative differences in growth dynamics of the same cells cultivated in two different three-dimensional systems.

Animals↗
PubMed1994

Age-dependent haematological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of halothane and nitrous oxide.

Anaesthetic staff chronically exposed to high occupational concentrations of halothane and nitrous oxide were tested for numerous haematological and cellular function parameters at the peak of the working season and after 3 weeks vacation. The analysis of data was performed to compare differences in subjects younger and older than the age of 40 years, respectively when compared with normal controls. The analysis revealed a higher recovery of erythrocyte count in the blood of older staff, and stronger disturbance of leucocyte formation in younger staff. In contrast, monocytes appeared to be more stable in the younger staff as were the T and B lymphocyte counts. After stimulation with PHA, Con A and PWM mitogens, lymphocytes from the older age group incorporated a significantly higher amount of tritiated thymidine, but stimulation indices did not differ. Natural killer cell numbers appeared equally affected; natural killer cell activity was unaffected, but there was an increase in activity in the younger staff after the vacation. Serum immunoglobulin concentrations tended to be more affected in older individuals at the peak of the working season.

Adult↗
PubMed1994

Survival analysis of untreated patients with non-small-cell lung cancer.

The survival rate analysis of 130 patients with non-small-cell lung cancer who did not receive any specific anticancer therapy showed no statistically significant differences in the survival rates between various TNM combinations classified into stage groups II, IIIa, IIIb, and IV, as proposed by Mountain in 1989 and adopted by the American Joint Committee on Cancer. Following these findings, based on survival probabilities, two distinctive staging groups could be distinguished. The first stage group was composed of only the T1, 2N0, M0 combination, and the second of all other TNM combinations. In a purely biologic sense of tumor growth, the lymph node involvement appeared to be the crucial factor determining the length of survival.

Adult↗
PubMed1994

Prognostic value of steroid hormone receptors concentration in patients with endometrial carcinoma.

The concentrations of progesterone receptors in endometrial tumors of 160 patients were analyzed with respect to survival and presence of clinicopathologic prognostic factors. The concentration of 25 fmol/mg of proteins for progesterone receptors appeared to be most powerful for prediction of survival. The survival was also significantly correlated to age, depth of myometrial invasion and clinical stage of the tumor. Concentration of estrogen receptors could not be correlated with the probability of patients' actuarial survival.

Actuarial Analysis↗
PubMed1994

Peripheral blood CD5+ B cell subset in the remission phase of systemic connective tissue diseases.

OBJECTIVE: To get a better insight into the level of circulating CD5+ B cells as related to the systemic connective tissue disease activity. METHODS: Peripheral blood CD5+CD19+ cells of patients in the remission phase of systemic lupus erythematosus (SLE) (n = 28), Sjögren's syndrome (SS) (n = 20), rheumatoid arthritis (RA) (n = 26), and 19 control healthy subjects were analyzed by 2-color flow cytometry. RESULTS: In comparison to control group, the patients with SLE had a significant increase in the relative CD19+CD5+ blood cell count (p < 0.0005); this count was also different from the finding in both RA (p < 0.005) and patients with SS (p < 0.05). In contrast, the proportion of B cells expressing CD5 (within an individual B cell population) was significantly increased in all the 3 diseases compared to healthy subjects (SLE, p < 0.0001; SS, p < 0.05; and RA, p < 0.01). In the multivariate discriminant analysis, a discriminant function defined by the CD19+CD5+ subset strongly discriminated SLE, SS and RA from the control, but also SLE from both SS and RA. CONCLUSION: Our findings demonstrated that, in relation to healthy control subjects, the blood CD5+ B subset tended to be elevated in the patients in the remission phase of systemic connective tissue diseases, particularly in SLE.

Adult↗
PubMed1994

Gonadectomy abrogates sex differences in the effectiveness of chemical carcinogenesis in mice.

Sham-gonadectomized and gonadectomized male and female mice were given methylcholanthrene s.c. to assess the influence of sex hormones on carcinogenesis. Gonadectomy decreased the concentration of the respective sex hormone and increased the concentration of the opposite sex hormone. The results showed that androgens enhanced the effectiveness of carcinogenesis, while estrogens had the opposite effect. Gonadectomy effectively abrogated the sex differences in tumor induction.

Animals↗
PubMed1993

Correlation of morphological FAB classification and immunophenotyping: value in recognition of morphological, cytochemical and immunological characteristics of mixed leukaemias.

Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML.

Acute Disease↗
PubMed1993

Hypersensitivity to Parietaria officinalis pollen in newcomers to the area with the plant.

Hypersensitivity to Parietaria officinalis (wall pellitory) pollen and other environmental allergens was studied in pollinosis patients allergic to P. officinalis pollen who were born in areas without P. officinalis and later moved to the city of Split, where P. officinalis is responsible for some 65% of pollinosis cases. Highly significant positive correlations were found for both the intensity of skin test reaction and concentration of specific serum IgE with the length of residence in the area. In contrast, the respective data on subjects hypersensitive to P. officinalis pollen allergen, but born and living in the area of Split, revealed a tendency to negative correlation between age and intensity of hypersensitivity to P. officinalis. A number of patients from both groups were tested for presence of serum IgE antibodies specific for 14 common environmental allergens. Hypersensitivity to P. officinalis pollen was associated with hypersensitivity to olive, mugwort, and birch pollen in newcomers; hypersensitivity to birch and, to some extent, olive pollen was significantly more frequent in newcomers than in autochthonous patients who were allergic to P. officinalis pollen. Regardless of whether the patients were autochthons or newcomers to the area with P. officinalis, hypersensitivity to P. officinalis mostly excluded hypersensitivity to Dermatophagoides farinae and D. pteronyssinus, and vice versa.

Adolescent↗
PubMed1993

Effects of hyperbaric oxygen on rat embryos.

The aim of the study was to investigate the toxic effects of hyperbaric oxygen (HBO) on rat embryos. Two groups of Fischer pregnant rats were exposed to oxygen at pressures of 324 and 426 kPa for 90 min per day for 5 consecutive days (8-12 days of gestation). The third group was exposed to normobaric oxygen for 12 h on the eighth day of gestation. Two control groups were used; the first was comprised of intact and the second of sham-treated animals. The HBO treatment did not significantly affect maternal weight gain or reduce litter size, nor did it induce any embryonic abnormalities. However, the fetal body weight was reduced and the placental weight increased in the groups exposed to HBO at pressures of 324 and 426 kPa. When female fetuses which had been exposed to oxygen at 324 or 426 kPa were compared to the intact control group, a reduction in wet weights of 9.2 (p < 0.05) and 12.1% (p < 0.01), respectively, was noted. Male fetuses exposed to oxygen at 324 and 426 kPa displayed a reduced body weight of 11.7 (p < 0.01) and 16.6% (p < 0.01), respectively. Placental weight was increased by 18.9 (p < 0.01) and 23.6% (p < 0.01) in the groups exposed to oxygen at 324 and 426 kPa, respectively. These data suggest that HBO, either at 324 or 426 kPa, is not potent at inducing malformations and that the largest embryotoxic effects are upon fetal body weight and placental weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Evaluation of criteria contributions for the classification of systemic lupus erythematosus.

The American Rheumatism Association (ACR) preliminary and revised criteria for classification of systemic lupus erythematosus (SLE) were evaluated for sensitivity and specificity in a population of 100 patients with SLE and 100 patients with other rheumatic diseases. Bayes' theorem was applied for evaluation of ARA criteria for the classification of SLE and a scoring system was developed which allows simple determination of the probability of SLE. The evaluation revealed considerable differences in values of the ARA criteria. The serologic tests and discoid lupus appeared to be the most distinctive criteria, while Raynaud's phenomenon, oral and nasal ulcers and arthritis were of little value. Comparison of SLE and control patients presenting the same number of criteria revealed that patients with SLE exhibit more distinctive criteria. This finding emphasizes the need for a quantitative evaluation of classification criteria.

Evaluation Studies as Topic↗