47 results on '"Hadzija M"'
Search Results
2. Defective thymic T cell activation by concanavalin A and anti-CD3 in autoimmune nonobese diabetic mice. Evidence for thymic T cell anergy that correlates with the onset of insulitis
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Zipris, D., Lazarus, A. H., Andrew R Crow, Hadzija, M., and Delovitch, T. L.
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Immunology ,Immunology and Allergy - Abstract
In nonobese diabetic (NOD) mice, T cells play a major role in mediating autoimmunity against pancreatic islet beta-cells. We and others previously reported that age-related alterations in the thymic and peripheral T cell repertoire and function occur in prediabetic NOD mice. To study the mechanism responsible for these T cell alterations, we examined whether a defect exists in the thymus of NOD mice at the level of TCR-mediated signaling after activation by Con A and anti-CD3. We found that thymocytes from NOD mice respond weakly to Con A- and anti-CD3-induced proliferation, compared with thymocytes from control BALB/c, BALB.B, (BALB.B x BALB.K)F1, C57BL/6, and nonobese non-diabetic mice. This defect correlates with the onset of insulitis, because it can be detected at 7 to 8 weeks of age, whereas younger mice displayed a normal T cell responsiveness. Thymic T cells from (NOD x BALB/c)F1 mice, which are insulitis- and diabetes-free, exhibit an intermediate stage of unresponsiveness. This T cell defect is not due to a difference in the level of CD3 and IL-2R expression by NOD and BALB/c thymocytes, and both NOD CD4+ CD8- and CD4- CD8+ mature thymic T cells respond poorly to Con A. BALB/c but not NOD thymic T cells respond to Con A in the presence of either BALB/c or NOD thymic APC, suggesting that the thymic T cell defect in NOD mice is intrinsic to NOD thymic T cells and is not due to an inability of NOD APC to provide a costimulatory signal. The defect can be partially reversed by the addition of rIL-2 to NOD thymocytes. To determine whether a defect in signal transduction mediates this NOD thymic T cell unresponsiveness, we tested whether these cells elevate their intracellular free Ca2+ ion concentration in response to Con A. An equivalent Con A-induced increase in Ca2+ ion concentration in both NOD and BALB/c thymocytes was observed, suggesting a normal coupling between the CD3 complex and phospholipase C in NOD thymocytes. In contrast to their low proliferative response to Con A or anti-CD3, NOD thymocytes respond normally (i.e., as do BALB/c thymocytes) to the combinations of PMA plus the Ca2+ ionophore ionomycin and PMA plus Con A but weakly to Con A plus ionomycin. Our data suggest that the age-related NOD thymocyte unresponsiveness to Con A and anti-CD3 results from a defect in the signaling pathway of T cell activation that occurs upstream of protein kinase C activation.
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- 1991
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3. Female headstart in key factors responsible for mitochondrial functioning as a protective mechanism towards hyperoxia oxidative injury
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Saric⁎, A., primary, Sobocanec, S., additional, Balog, T., additional, Popovic Hadzija, M., additional, Kusic, B., additional, and Marotti et al, T., additional
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- 2012
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4. Lipid-bound sialic acid concentration in mice with myeloid leukemia and alloxan diabetes
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Hadzija M, Radacić M, Lipovac, Mirjana Gavella, Sverko, and Slijepcević M
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Male ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Mice, Inbred Strains ,Biochemistry ,Diabetes Mellitus, Experimental ,Mice ,chemistry.chemical_compound ,Endocrinology ,Diabetes mellitus ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Animals ,Insulin ,Chemistry ,Biochemistry (medical) ,Myeloid leukemia ,nutritional and metabolic diseases ,General Medicine ,Lipid Metabolism ,medicine.disease ,Sialic acid ,myeloid leukemia ,diabetes ,sialic acid ,carbohydrates (lipids) ,Methotrexate ,Leukemia, Myeloid ,Alloxan diabetes ,Sialic Acids - Abstract
Lipid-bound sialic acid concentration in mice with myeloid leukemia and alloxan diabetes
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- 1993
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5. Managing Chemical and Biological Agents
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RUDER BOSKOVIC INST ZAGREB (CROATIA), Hadzija, M., Furic, K., Pepeljnjak, S., Petranovic, M., Vucemilovic, A., RUDER BOSKOVIC INST ZAGREB (CROATIA), Hadzija, M., Furic, K., Pepeljnjak, S., Petranovic, M., and Vucemilovic, A.
- Abstract
Though the Biological Weapons Convention (BWC) prohibits the development production and stockpiling of biological and toxin weapons, during the war in Croatian we saw unknown artificial materials, which appeared to be like spider cobwebs. We expect that during the peace time domestic and international acts of terrorism may use chemical and biological pathogens with such an ideal delivery device as the cobweb with their polyvalent characteristics. Today the terrorists use very sophisticate chemical and biological weapons and such as anthrax, sarin or cyanides. In our approach we review delivery device and packaging of biological agents, and we address the technical difficulties in maintaining chemical and biological agents., Original contains color plates: All DTIC reproductions will be in black and white. Pres: The First World Congress on Chemical and Biological Terrorism, Dubrovnik, Croatia, 21-27 Apr 2002. Abstract only. p400 This article is from ADA411272 Chemical and Biological Medical Treatment Symposium - Industry II World Congress on Chemical and Biological Terrorism
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- 2001
6. Short-term effect of acarbose on specific intestinal disaccharidase activities and hyperglycaemia in CBA diabetic mice
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Juretic, D., primary, Bernik, S., additional, Cop, L., additional, Hadzija, M., additional, Petlevski, R., additional, and Lukac-Bajalo, J., additional
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- 2003
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7. Amylin-Induced Cytotoxicity Is Associated with Activation of Caspase-3 and MAP Kinases
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Rumora, L., primary, Hadzija, M., additional, Bariic, K., additional, Maysinger, D., additional, and Grubiic, T. Zanic, additional
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- 2002
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8. Naturally processed heterodimeric disulfide-linked insulin peptides bind to major histocompatibility class II molecules on thymic epithelial cells.
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Forquet, F, primary, Hadzija, M, additional, Semple, J W, additional, Speck, E, additional, and Delovitch, T L, additional
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- 1994
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9. RESISTANCE OF HUMAN and MOUSE MYELOID LEUKEMIA CELLS TO UV RADIATION.
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Poljak-Blazi, Marija, Osmak, Maja, and Hadzija, M.
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- 1989
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10. Effect of `antidiabetis` herbal preparation on serum glucose and fructosamine in NOD mice
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Petlevski, R., Hadzija, M., Slijepcevic, M., and Juretic, D.
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- 2001
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11. Molecular mechanisms involved in the antiproliferative action of protein tyrosine phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate
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Ban, J., Maysinger, D., Kovac, V., Galetic, I., Matulic, M., Hadzija, M., and Uzarevic, B.
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- 2000
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12. An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma.
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Katić, M, Hadzija, M, Wrischer, M, and Pavelić, K
- Abstract
The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet beta cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor alpha (TGFalpha). Normal Langerhans islets, when grown in culture, are viable for 2-3 weeks. After treatment with TGFalpha, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected beta cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected beta cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of beta cell transformation and, therefore, could represent 'early events' in the multistep carcinogenesis of insulinomas.
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- 1999
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13. Recovery of the immune system in diabetic mice after transplantation of isolated islets of Langerhans
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Sverko, M. Poljak-Blazi, Slijepcević M, Hadzija M, and T. Marotti
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Cell ,Islets of Langerhans Transplantation ,Spleen ,Biology ,Diabetes Mellitus, Experimental ,diabetes ,transplantation ,Islet transplantation ,immune system ,experimental diabetes ,pancreatic islet isolation ,Islets of Langerhans ,Mice ,Immune system ,Internal medicine ,Internal Medicine ,medicine ,Animals ,geography ,Mice, Inbred C3H ,geography.geographical_feature_category ,Insulin ,Islet ,Transplantation ,Transplantation, Isogeneic ,medicine.anatomical_structure ,Endocrinology ,Immune System ,Collagenase ,Female ,Digestion ,medicine.drug - Abstract
Adult CBA/HZgb mice islets harvested by collagenase digestion were injected intraperitoneally in 52 singeneic diabetic recipients (CBA/Hgb leads to CBA/HZgb, 450-600 islets per mouse). Normal serum glucose levels, 24-h urine volume, insulin levels and body weight were completely restored to normal in all recipients during the next 2-5 months. Immunological function was assessed in control, diabetic and diabetic-transplanted mice by following their responses to sheep erythrocytes (expressed as the number plaque-forming cells in the spleen). In transplanted mice, the plaque-forming cell responses were as follows: 1 month after transplantation--43% of the plaque-forming cell counts in control (normal, non-diabetic) mice; 2 months after transplantation--56% of the control value; and 94% of the control value after 5 months. Ten months after the transplantation, the plaque-forming cell counts were slightly above the control value (148%). It appears, therefore that transplantated islet tissue positively affects the immunological as well as the diabetic state of the recipients.
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- 1984
14. Influence of the thymus extract on the immunological function of animals with experimental diabetes
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Hadzija M, M. Poljak-Blazi, V. Sverko, and Slijepcević M
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medicine.medical_specialty ,Ratón ,Endocrinology, Diabetes and Metabolism ,Lymphocyte ,medicine.medical_treatment ,Clinical Biochemistry ,Spleen ,chemical and pharmacologic phenomena ,Biology ,Biochemistry ,thymus ,diabetes ,immunology ,Endocrinology ,Immune system ,Diabetes mellitus ,Internal medicine ,medicine ,Thymus extract ,Insulin ,Biochemistry (medical) ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,medicine.anatomical_structure ,Immunization ,Immunology - Abstract
After immunization with SRBC, the number of plaque-forming cells (PFC) in the spleen of alloxan-diabetic mice, in nondiabetic TIR mice and in alloxan-diabetic TIR mice was significantly decreased as compared with control non-diabetic donors. The ability of lymphocytes from alloxan-diabetic mice to adoptively restore the suppressed immune response of TIR mice, was reduced in comparison with the effect of lymphocytes from normal, nondiabetic donors. Local GVH reaction in nondiabetic rat recipients provoked by lymphocytes from control healthy mice was 5.6 +/- 0.7 mm. Significantly lower rate of local GVH reaction after injection of lymphocytes from diabetic donors was found in diabetic as in nondiabetic recipients as well. Treatment of alloxan-diabetic mice with thymus extract or with insulin, partly restored depressed function of the humoral and cellular system. Treatment of diabetic mice with both thymus extract and insulin, was even more effective in restoring of their immune reactivity. Diabetic condition strongly influenced the function of the immune system. This could be attributed to depletion of T-lymphocytes, changed relations between the lymphocyte subpopulations in diabetic donors, and disturbance of lymphocyte metabolism.
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- 1987
15. Influence of antigen processing on thymic T-cell selection
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Hadzija, M., Semple, J.W., and Delovitch, T.L.
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- 1991
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16. Comparisn of sensitivity of bone marrow cells and myeloid leukaemia cells to ultraviolet irradiation
- Author
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Poljak-Blaẑi, M. and Hadẑija, M.
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- 1987
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17. Mononucleotide repeats in the SMAD4 gene promoter in colon carcinoma tissue of Croatian patients.
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Nikolic A, Cacev T, Aralica G, Popovic Hadzija M, Kapitanovic S, and Radojkovic D
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- Adult, Aged, Aged, 80 and over, Cell Transformation, Neoplastic genetics, Croatia, Female, Haplotypes genetics, Humans, Male, Middle Aged, Adenocarcinoma genetics, Colonic Neoplasms genetics, Promoter Regions, Genetic genetics, Smad4 Protein genetics
- Abstract
This study was aimed at the analysis of mononucleotide repeats -462T(15) and -4T(12) in the SMAD4 gene promoter in sporadic colon adenocarcinoma tissue of Croatian patients. The analysis has included 60 pairs of samples of colon tumor and adjacent normal tissue. The number of thymidines in the tracts -462T(15) and -4T(12) of the SMAD4 gene promoter was determined by PCR with fluorescently labeled primers followed by the analysis of obtained DNA fragments by capillary electrophoresis. In the normal colon tissue two haplotypes were present: -462T(15)/-4T(12) in 51 patients (85%) and -462T(16)/-4T(12) in 9 patients (15%). Among the cases with haplotype -462T(15)/-4T(12) detected in normal colon tissue, in 5 cases (8%) malignant tissue displayed different haplotypes: 462T(10)/-4T(10), -462T(12)/-4T(12), 462T(13)/-4T(11), -462T(14)/-4T(10) and -462T(15)/-4T(11). Haplotype -462T(14)/-4T(10) was previously found to be associated with significantly decreased SMAD4 gene promoter activity in comparison to the wild type, while the other detected haplotypes remain to be functionally characterized. This study has shown that functionally relevant somatic alterations of the SMAD4 gene promoter are found in some colon cancer tumors. Although not as frequent in colon as in pancreatic cancer, they may be of significance for certain cases and their role in colon tumorigenesis should be investigated further., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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18. Alzheimer's disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes.
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Mustapic M, Popovic Hadzija M, Pavlovic M, Pavkovic P, Presecki P, Mrazovac D, Mimica N, Korolija M, Pivac N, and Muck-Seler D
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- Aged, Aged, 80 and over, Alleles, Alzheimer Disease complications, Alzheimer Disease epidemiology, Croatia epidemiology, DNA genetics, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Female, Gene Frequency, Genotype, Heterozygote, Humans, Logistic Models, Male, Risk Factors, Alzheimer Disease genetics, Apolipoproteins E genetics, Diabetes Mellitus, Type 2 genetics, Polymorphism, Genetic genetics, Tumor Necrosis Factor-alpha genetics
- Abstract
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-α) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-α gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-α gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-α gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.
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- 2012
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19. Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with Type 1 Diabetes in Croatians.
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Korolija M, Renar IP, Hadzija M, Medvidović EP, Pavković P, Jokić M, and Hadzija MP
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- Adenine, Adult, Age of Onset, Blood Glucose analysis, CTLA-4 Antigen, Croatia, Cytosine, DNA Primers, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 epidemiology, Genetic Variation, Genotype, Glycated Hemoglobin analysis, Guanine, Humans, Polymerase Chain Reaction, Reference Values, Risk Assessment, Thymine, Antigens, CD genetics, Diabetes Mellitus, Type 1 genetics, Polymorphism, Genetic, Polymorphism, Single Nucleotide
- Abstract
In this case-control study the association between the PTPN22 1858T and CTLA-4 49G gene variants and T1D in Croatian population was examined. We found that distribution of PTPN22 C1858T and CTLA-4 A49G genotypes between T1D patient (n=102) and control (n=193) groups differ significantly (p<0.0001 and p=0.012, respectively). Moreover, although the risk alleles of both SNPs are distributed more frequently in patients, the significant difference is observed only for PTPN22 1858T allele (p<0.0001). This is therefore the first evidence that analyzed gene variants contribute to T1D pathogenesis in Croatian population.
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- 2009
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20. Skin decontamination with mineral cationic carrier against sarin determined in vivo.
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Vucemilović A, Hadzija M, and Jukić I
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- Animals, Mice, Mice, Inbred NOD, Skin, Chemical Warfare Agents toxicity, Cholinesterase Inhibitors toxicity, Decontamination, Sarin toxicity, Zeolites therapeutic use
- Abstract
Our Institute's nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In this in vivo study, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC was administered immediately after contamination. The results showed that decontamination with MCC could achieve therapeutic efficacy corresponding to 3 x LD(50) of percutaneous sarin and call for further research.
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- 2009
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21. Efficacy of mineral cationic carrier against sulphur mustard in skin decontamination.
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Vucemilović A, Hadzija M, and Jukić I
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- Animals, Lethal Dose 50, Mice, Mice, Inbred CBA, Chemical Warfare Agents poisoning, Decontamination, Mustard Gas poisoning, Skin drug effects
- Abstract
The aim of this study was to evaluate decontamination (absorption) efficacy of a preparation called Mineral Cationic Carrier (MCC) against skin contamination with sulphur mustard in vivo. MCC is a synthetic preparation with known ion exchange, absorption efficiency, and bioactive potential. CBA mice were applied increasing doses of sulphur mustard on their skin and MCC was administered immediately after skin contamination. The results have confirmed the decontamination efficacy of MCC preparation, corresponding to 8.4 times the LD50 of percutaneous sulphur mustard, and call for further investigation.
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- 2008
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22. Toxicological assessment of P-9801091 plant mixture extract after chronic administration in CBA/HZg mice--a biochemical and histological study.
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Petlevski R, Hadzija M, Slijepcević M, and Juretić D
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- Animals, Blood Chemical Analysis, Kidney drug effects, Liver drug effects, Lung drug effects, Male, Mice, Mice, Inbred CBA, Pancreas drug effects, Spleen drug effects, Testis drug effects, Hypoglycemic Agents toxicity, Plant Extracts toxicity
- Abstract
Acute, subchronic and chronic effects of the P-9801091 plant mixture extract at a dose of 20 mg/kg body mass were assessed in serum of healthy CBA/HZg mice at 24 hours, 7 days, 3 months and 6 months of treatment (experimental group), and compared with the values obtained in the control group of untreated healthy CBA/HZg mice. The P-9801091 plant mixture extract is an antihyperglycemic preparation containing Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli fructus sine semine (Phaseolus vulgaris L.), Millefolii herba (Achillea millefolium L.), Mori folium (Morus nigra L.), Valerianae radix (Valeriana officinalis L.) and Urticae herba et radix (Urtica dioica L). Toxic effect of the P-9801091 plant mixture extract was assessed by the following biochemical parameters: urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cholesterol. Also, histopathological examination of the kidneys, liver, spleen, pancreas, testes and lungs was performed. Results of biochemical testing performed at specified time points generally showed no statistically significant differences from control values, with the only exception of the catalytic concentration of AST in the experimental group measured on day 7, which was significantly increased as compared with the control group (p<0.05). Pathohistological examination including characteristic organ and tissue structure, and parenchyma relationship to the adjacent blood vessels and connective tissue in the examined organs revealed no major pathologic changes.
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- 2008
23. K-ras and Dpc4 mutations in chronic pancreatitis: case series.
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Popović Hadzija M, Korolija M, Jakić Razumović J, Pavković P, Hadzija M, and Kapitanović S
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- Genes, p53 genetics, Humans, Pancreatitis, Chronic pathology, Genes, ras genetics, Mutation genetics, Pancreatitis, Chronic genetics, Smad4 Protein genetics
- Abstract
Aim: To assess whether alterations in the K-ras, p53, and DPC4 genes are present in pancreatitis, a potential precancerous condition that can progress to pancreatic adenocarcinoma. To investigate the alterations occurring at hot spots of K-ras (exon 1), p53 (exons 5 and 7), and DPC4 (exons 8, 10 and 11)., Methods: In 10 patients with acute and 22 with chronic pancreatitis, without pancreatic intraepithelial neoplasia (PanIN), DNA was isolated from paraffin embedded tissue samples. The extracted DNA was analyzed by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, single-strand conformation polymorphism (SSCP) analysis, and DNA sequencing., Results: In acute pancreatitis samples no mutations were found in any of the investigated genes. In 7 out of 22 samples of chronic pancreatitis nucleotide substitution at exon 1 of K-ras (five at codon 12 and two at codon 13) were found. No mutations in p53 (exons 5 and 7) were detected. Two samples had nucleotide substitutions at exons 8 and 11 of DPC4, introducing STOP signal and change in the amino acid sequence, respectively. One chronic pancreatitis sample displayed simultaneous mutations in K-ras (exon 1, codon 12) and DPC4 (exon 8, codon 358)., Conclusion: Mutations of K-ras and Dpc4 genes can accumulate already in non-malignant, inflammatory pancreatic tissue, suggesting its applicability in monitoring of further destruction of pancreatic tissue and progression into malignancy.
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- 2007
24. Effect of acarbose on alanine aminotransferase and aspartate aminotransferase activities in the liver of control and diabetic CBA mice.
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Petlevski R, Hadzija M, Bajalo JL, and Juretić D
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- Alloxan, Animals, Diabetes Mellitus, Experimental drug therapy, Liver enzymology, Male, Mice, Mice, Inbred CBA, Acarbose pharmacology, Alanine Transaminase metabolism, Aspartate Aminotransferases metabolism, Diabetes Mellitus, Experimental enzymology, Hypoglycemic Agents pharmacology, Liver drug effects
- Abstract
The purpose of this study was to examine the short-term effects of diet containing 0.1% (m/m) of acarbose in standard laboratory chow on specific liver enzyme activities: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in control and diabetic CBA mice. Diabetes was induced by intravenous injection of alloxan monohydrate in a dose of 75 mg kg(-1) mouse body mass seven days before the treatment with acarbose. There were four groups of CBA mice in the experiment: control (C) mice (n = 6) and diabetic (D) mice (n = 8) fed standard chow; control (C/A-100) mice (n = 8) and diabetic (D/A-100) mice (n = 8) fed standard chow containing 0.1% acarbose. Diabetes induced a decrease of the ALT catalytic activities to 69.6% of the control value. A similar level of decreased ALT catalytic activity was detected in the liver of control and diabetic mice fed chow containing 0.1% acarbose. No changes in the specific and total activities of AST in the liver of experimental groups were observed.
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- 2006
25. nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma.
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Kapitanović S, Cacev T, Berković M, Popović-Hadzija M, Radosević S, Seiwerth S, Spaventi S, Pavelić K, and Spaventi R
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- Adenocarcinoma mortality, Adenocarcinoma pathology, Aged, Biomarkers, Tumor analysis, Colonic Neoplasms mortality, Colonic Neoplasms pathology, DNA, Neoplasm genetics, Female, Genes, Tumor Suppressor physiology, Humans, Immunohistochemistry methods, Male, NM23 Nucleoside Diphosphate Kinases, Neoplasm Staging, Polymerase Chain Reaction methods, RNA, Messenger analysis, RNA, Neoplasm analysis, Survival Analysis, Adenocarcinoma genetics, Colonic Neoplasms genetics, Loss of Heterozygosity genetics, Nucleoside-Diphosphate Kinase analysis
- Abstract
Background: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene., Aims: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression., Materials/methods: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real time" RT-PCR., Results: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours., Conclusions: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis.
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- 2004
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26. Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen).
- Author
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Rumora L, Hadzija M, Maysinger D, and Zanić-Grubisić T
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- Animals, Cell Line, Cell Survival, Dual Specificity Phosphatase 1, Enzyme Activation, Enzyme Inhibitors metabolism, JNK Mitogen-Activated Protein Kinases metabolism, Protein Phosphatase 1, Rats, p38 Mitogen-Activated Protein Kinases metabolism, Cell Cycle Proteins metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Immediate-Early Proteins metabolism, Organometallic Compounds metabolism, Phenanthrolines metabolism, Phosphoprotein Phosphatases metabolism, Protein Tyrosine Phosphatases metabolism, Vanadium metabolism
- Abstract
Lower micromolar concentrations of peroxovanadium compound potassium bisperoxo(1,10-phenanthroline)oxovanadate (V) [bpV (phen)] stimulate RINm5F cell metabolic activity. 1 and 3 micromol/L bpV (phen) induces strong and sustained activation of extracellular signal-regulated kinase (ERK). However, it seems that bpV (phen) does not effect c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In addition, bpV (phen) induces mitogen-activated protein kinase phosphatase-1 (MKP-1) expression. We found that ERK activation could be completely abolished if RINm5F cells were incubated with both bpV (phen) and PD 98059, a specific inhibitor of upstream ERK kinase MEK1. On the other hand, this combined treatment up-regulated activation of stress kinases, JNK and p38 MAPK, significantly suppressed MKP-1 expression and induced cell death. Thus, our results suggest that the mechanism underlying bpV (phen) survival-enhancing effect could be associated with induced ERK activation and MKP-1 expression.
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- 2004
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27. Infrequent alteration of the DPC4 tumor suppressor gene in renal cell carcinoma.
- Author
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Popović Hadzija M, Hrasćan R, Bosnar MH, Zeljko Z, Hadzija M, Cadez J, Pavelić K, and Kapitanović S
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- Female, Humans, Loss of Heterozygosity, Male, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single-Stranded Conformational, Smad4 Protein, Carcinoma, Renal Cell genetics, DNA-Binding Proteins genetics, Kidney Neoplasms genetics, Trans-Activators genetics
- Abstract
The aim of this study was to investigate the alterations in the DPC4 tumor suppressor gene in renal cell carcinoma (RCC). The study included 32 tumor specimens from Croatian patients with a diagnosis of RCC. Loss of heterozygosity (LOH) was investigated using three specific oligonucleotide primers for the three DPC4 polymorphic markers. Our investigation of mutations in the DPC4 gene was focused on exons 2, 8, 10 and 11. These exons belong to the mad homology domains 1 (exon 2) and 2 (exons 8-11). The presence of previously documented mutation in exons 2 (codon 100), 8 (codon 358), 10 (codon 412), and 11 (codon 493) was investigated by restriction fragment length polymorphism (RFLP) analysis, as a first screening method. Finally, the study was extended to search for any other type of mutation in the four selected exons by single strand conformation polymorphism (SSCP) assay. To increase heterozygosity, all 32 tumor specimens were tested with primers for three polymorphic markers. A total of 30 (94%) were heterozygous (informative). LOH at any of these markers was only revealed in four (13%) of the 30 informative samples. No tumor samples were positive for mutation in the four investigated exons analyzed by RFLP. In addition, no samples showed other types of mutation in denaturing conditions. Genetic alterations were shown only in a minority of patients, probably because mutation analysis of the DPC4 gene has only been partially covered by our work. It seems that exon 2 (belonging to the MH1 domain) and exons 8, 10, 11 (belonging to the MH2 domain) are not altered in RCC. This investigation must be extended on other exons of DPC4 for a better understanding a role of this gene in renal cell carcinoma.
- Published
- 2004
- Full Text
- View/download PDF
28. Status of the DPC4 tumor suppressor gene in sporadic colon adenocarcinoma of Croatian patients: identification of a novel somatic mutation.
- Author
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Popović Hadzija M, Radosevic S, Kovacević D, Lukac J, Hadzija M, Spaventi R, Pavelić K, and Kapitanović S
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Chromosomes, Human, Pair 18 genetics, Croatia epidemiology, DNA Mutational Analysis, DNA, Neoplasm genetics, Female, Genes, Tumor Suppressor, Humans, Male, Microsatellite Repeats, Middle Aged, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single-Stranded Conformational, Smad4 Protein, Colorectal Neoplasms genetics, DNA-Binding Proteins genetics, Gene Expression Regulation, Neoplastic, Loss of Heterozygosity, Mutation genetics, Trans-Activators genetics
- Abstract
Loss of heterozygosity (LOH) of loci on chromosome 18q occurs in a majority of colorectal cancers. The DPC4 (Smad4) tumor suppressor gene, located at 18q21.1, may be a predisposing gene for Juvenile Polyposis Syndrome. To investigate alterations of the DPC4 gene in sporadic colon adenocarcinoma, a panel of 60 tumor specimens from Croatian patients was surveyed for evidence of LOH and also for mutations within the entire DPC4 coding region (exons 1-11). Using three pairs of specific primers for the three DPC4 microsatellite repetitive sequences, we investigated the frequency of LOH. The presence of single nucleotide change at restriction sites of specific codons in exons 2, 8, 10, and 11 (which belong to the conserved region of the gene) was examined by RFLP analysis. The investigation was extended to search for any other mutation within the entire coding region of the DPC4 gene by single strand conformation polymorphism (SSCP) analysis. Our results show a high frequency of heterozygosity in 58 of 60 (97%) colon adenocarcinoma samples. LOH at any one of the three flanking markers was observed in 26 (45%) of the 58 informative cases. The loss of one allele of the DPC4 gene was negatively correlated with tumor size; more frequent in smaller tumors (<5 cm) than in larger ones. A mutation was found in exon 11 in only one tumor sample (T18), and the mutation was verified by sequencing. Sequencing demonstrated a novel mutation-a deletion in exon 11 (134-153 del TAGACGAAGTACTTCATACC) of the DPC4 gene in the MH2 domain. These data suggest that inactivation of the DPC4 gene contributes to the genesis of colorectal carcinoma through allelic loss whereas mutation in the coding region of the DPC4 gene is infrequently detected in Croatian patients with A, B or C stages of colorectal cancers.
- Published
- 2004
- Full Text
- View/download PDF
29. Differing effects of two iron compounds on experimental arthritis, TNF-alpha levels and immune response in mice.
- Author
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Poljak-Blazi M, Hrvacić B, Zupanović Z, Hadzija M, Stanić B, and Polancec D
- Subjects
- Animals, Arthritis, Experimental chemically induced, Arthritis, Experimental immunology, Autoimmunity drug effects, Cell Division drug effects, Cells, Cultured, Citric Acid administration & dosage, Citric Acid pharmacokinetics, Citric Acid therapeutic use, Disease Models, Animal, Drug Administration Schedule, Drug Combinations, Ferric Compounds administration & dosage, Ferric Compounds adverse effects, Ferric Compounds pharmacokinetics, Injections, Intramuscular, Iron Compounds administration & dosage, Iron Compounds chemistry, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Serum Albumin, Bovine administration & dosage, Serum Albumin, Bovine immunology, Sorbitol administration & dosage, Sorbitol pharmacokinetics, Sorbitol therapeutic use, Spleen cytology, Spleen drug effects, Thymus Gland cytology, Thymus Gland drug effects, Tumor Necrosis Factor-alpha drug effects, Tumor Necrosis Factor-alpha metabolism, Arthritis, Experimental drug therapy, Autoimmunity immunology, Iron Compounds therapeutic use, Tumor Necrosis Factor-alpha immunology
- Abstract
The effects of ferric-sorbitol-citrate and ferric-citrate on the severity of experimental arthritis, TNF-alpha secretion and the immune status were examined in mice. Arthritis was induced by footpad injection of methylated BSA and intraperitoneal injection of Bordetella pertussis. Joint and footpad swelling were measured weekly by a caliper. TNF-alpha serum levels were measured by ELISA. The immune status was determined by the response of mouse lymphocytes to ConA in vitro and by the antigen-presenting cell assay. Experimental arthritis was aggravated by ferric-citrate, whereas ferric-sorbitol-citrate did not promote it. If applied to normal (non-arthritic) mice three times a week for 4 weeks, ferric-sorbitol-citrate stimulated isolated splenocytes to increase production of TNF-alpha, the function of antigen-presenting cells and lymphocyte proliferation in response to ConA in vitro. TNF-alpha production by cultured splenocytes was also stimulated. In mice with antigen-induced arthritis, iron compounds did not additionally stimulate TNF-alpha production. Thus, we have shown that ferric-sorbitol-citrate stimulated TNF-alpha production, antigen-presenting cell activity and cellular immune response. Development of antigen-induced arthritis and TNF-alpha production in arthritic mice were not stimulated.
- Published
- 2003
- Full Text
- View/download PDF
30. Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091.
- Author
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Petlevski R, Hadzija M, Slijepcević M, Juretić D, and Petrik J
- Subjects
- Animals, Glutathione Transferase drug effects, Hyperglycemia drug therapy, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents therapeutic use, Lipid Peroxidation drug effects, Male, Malondialdehyde metabolism, Mice, Mice, Inbred NOD, Plant Extracts administration & dosage, Plant Extracts therapeutic use, Hypoglycemic Agents pharmacology, Liver drug effects, Phytotherapy, Plant Extracts pharmacology, Plants, Medicinal
- Abstract
Changes in the concentration of glutathione S-transferases (GSTs) and malondialdehyde (MDA) were assessed in the liver of normal and diabetic NOD mice with and without treatment with the plant extract P-9801091. The plant extract P-9801091 is an antihyperglycaemic preparation containing Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum of fi cinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris L.), Millefoliiherba (Achillea millefolium L.), Mori folium (Morus nigra L.), Valerianae radix (Valeriana of ficinalis L.) and Urticae herba et radix (Urtica dioica L). Hyperglycaemia in diabetes mellitus is responsible for the development of oxidative stress (via glucose auto-oxidation and protein glycation), which is characterized by increased lipid peroxide production (MDA is a lipid peroxidation end product) and/or decreased antioxidative defence (GST in the liver is predominantly an alpha enzyme, which has antioxidative activity). The catalytic concentration of GSTs in the liver was significantly reduced in diabetic NOD mice compared with normal NOD mice (p < 0.01), while the concentration of MDA showed a rising tendency (not significant). The results showed that statistically significant changes in antioxidative defence occurred in the experimental model of short-term diabetes mellitus. A 7-day treatment with P-9801091 plant extract at a dose of 20 mg/kg body mass led to a significant increase in the catalytic concentration of GSTs in the liver of diabetic NOD mice (p < 0.01) and a decrease in MDA concentration (not significant), which could be explained by its antihyperglycaemic effect., (Copyright 2003 John Wiley & Sons, Ltd.)
- Published
- 2003
- Full Text
- View/download PDF
31. Aberration of FHIT gene is associated with increased tumor proliferation and decreased apoptosis-clinical evidence in lung and head and neck carcinomas.
- Author
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Pavelić K, Krizanac S, Cacev T, Hadzija MP, Radosević S, Crnić I, Levanat S, and Kapitanović S
- Subjects
- Adult, Aged, Apoptosis genetics, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Division genetics, Chromosome Fragility genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, DNA, Neoplasm genetics, Female, Gene Expression, Genes, Tumor Suppressor, Head and Neck Neoplasms metabolism, Humans, Immunohistochemistry, Loss of Heterozygosity, Lung Neoplasms metabolism, Male, Middle Aged, Neoplasm Proteins metabolism, Prognosis, Acid Anhydride Hydrolases, Head and Neck Neoplasms genetics, Head and Neck Neoplasms pathology, Lung Neoplasms genetics, Lung Neoplasms pathology, Mutation, Neoplasm Proteins genetics
- Abstract
Background: Human FHIT (fragile histidine triad) gene is highly conserved gene homologous to a group of genes identified in prokaryotes and eukaryotes. Loss of FHIT function may be important in the development and/or progression of various types of cancer., Materials and Methods: We undertook a clinical study to analyze the relation between aberrant function of FHIT gene, tumor cell proliferation, and intensity of apoptosis as well as prognostic output in lung and squamous cell head and neck carcinoma (HNSCC). Status of FHIT gene, expression of p21waf1, intensity of apoptosis, and cell proliferation were analyzed in HNSCC and lung carcinoma tissues by molecular genetic methods, immunohistochemistry, [3H]-thymidine labeling method, and FACScan analysis in frozen and paraffin-embedded tissue sections., Results: The majority of the malignant lung and HNSCC lesions displayed aberrant expression of FHIT gene, followed by low or negative expression of p21waf1, and increased intensity of cell proliferation. Similar results were obtained on synchronous combinations of normal, precancerous, and cancerous head and neck tissues. The observed changes increased with progression of these lesions. We examined tumor and corresponding normal tissue samples for microsatellite markers D3S1300 and D3S4103 to evaluate the loss of heterozygosity (LOH) at the FHIT gene loci. We found high percentage of LOH in both lung tumors and HNSCC (75% for D3S1300 and 79% for D3S4103 in lung cancer, and 87% for D3S1300 and 78% for D3S4103 in HNSCC). The median survival time of the patients suffering from lung cancer without FHIT protein expression was 22.46 months and that of the patients with FHIT expression 36.04 months. FHIT-negative cases tended to correlate with a worse prognosis, but this was not statistically significant. Median survival time of HNSCC patients without FHIT protein expression was 30.86 months and that of the patients with FHIT expression was 64.04 months (p < 0.05)., Conclusions: Our results show a correlation between aberrant FHIT expression, a low rate of apoptosis, and high tumor cell proliferation. Aberrant FHIT gene could be a prognostic marker in lung cancer.
- Published
- 2001
32. Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice.
- Author
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Petlevski R, Hadzija M, Slijepcevic M, and Juretic D
- Subjects
- Animals, Diabetes Mellitus, Type 1 blood, Male, Mice, Mice, Inbred NOD, Acarbose therapeutic use, Blood Glucose analysis, Diabetes Mellitus, Type 1 drug therapy, Fructosamine blood, Hypoglycemic Agents therapeutic use, Phytotherapy, Plant Extracts therapeutic use
- Abstract
The antihyperglycemic effect of the Antidiabetis herbal preparation ((Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris), Millefollii herba (Achillea millefolium L.), Morii folium (Morus nigra L.), Valeriane radix (Valleriana officinalis L.), Urticae herba et radix (Urtica dioica L.)), patent No. P-9801091 Zagreb, Croatia was investigated. Two extracts were prepared: ethanol extract (extract 1), and ethanol extract from which ethanol was evaporated on a rotatory evaporator at a temperature of 45 degrees C (extract 2). Extract 1 and extract 2 were administered (in experiment 1) to alloxan-induced non-obese diabetic (NOD) mice in the same dose of 20 mg/kg. Blood glucose was determined before, and 10, 30, 60 and 120 min after the preparation administration. Extract 1 and extract 2 decreased the level of blood glucose by 10 and 20%, respectively, of the initial value (at 0 min, mean = 22.6 +/- 8.3 mmol/l). Serum levels of glucose and fructosamine were determined in NOD mice, NOD mice administered extract 2 in a dose of 20 mg/kg of extract 2, and NOD mice administered acarbose in a dose of 25 mg/100 g chow, in order to verify the hypoglycemic action of extract 2 (in experiment 2). Extract 2 and acarbose were admixed to the chow. The duration of treatment was 7 days. Significantly lower glucose (P < 0.05) and fructosamine (P < 0.001) levels were recorded in extract 2 treated NOD mice as compared with NOD mice. Study results showed extract 2 to significantly decrease the level of glucose and fructosamine in alloxan induced NOD mice. Our future studies will be focused on the search of active principles of the extracts.
- Published
- 2001
- Full Text
- View/download PDF
33. Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer.
- Author
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Had ija MP, Kapitanović S, Radosević S, Cacev T, Mirt M, Kovacević D, Cacev T, Hadzija M, Spaventi R, and Pavelić K
- Subjects
- Aged, Aged, 80 and over, Female, Genes, Tumor Suppressor, Heterozygote, Humans, Male, Middle Aged, Smad4 Protein, Colonic Neoplasms genetics, DNA-Binding Proteins genetics, Trans-Activators genetics
- Abstract
We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.
- Published
- 2001
- Full Text
- View/download PDF
34. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy.
- Author
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Pavelić K, Hadzija M, Bedrica L, Pavelić J, Dikić I, Katić M, Kralj M, Bosnar MH, Kapitanović S, Poljak-Blazi M, Krizanac S, Stojković R, Jurin M, Subotić B, and Colić M
- Subjects
- Adjuvants, Pharmaceutic adverse effects, Adjuvants, Pharmaceutic pharmacology, Aging physiology, Animals, Apoptosis drug effects, Body Weight drug effects, Cell Cycle Proteins analysis, Cell Division drug effects, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclins analysis, Dog Diseases drug therapy, Dog Diseases pathology, Dogs, Female, HeLa Cells, Humans, Male, Melanoma, Experimental drug therapy, Melanoma, Experimental pathology, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Neoplasms pathology, Neoplasms veterinary, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar, Signal Transduction drug effects, Tumor Cells, Cultured, Tumor Suppressor Proteins analysis, Zeolites adverse effects, Zeolites pharmacology, Adjuvants, Pharmaceutic therapeutic use, Neoplasms drug therapy, Protein Serine-Threonine Kinases, Zeolites therapeutic use
- Abstract
Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.
- Published
- 2001
- Full Text
- View/download PDF
35. Involvement of lipid peroxidation, oncogene expression and induction of apoptosis in the antitumorous activity of ferric-sorbitol-citrate.
- Author
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Poljak-Blazi M, Kralj M, Hadzija MP, Zarković N, Zarković K, and Waeg G
- Subjects
- Aldehydes metabolism, Caco-2 Cells, Drug Combinations, Genes, p53, Humans, Proto-Oncogene Proteins c-bcl-2 physiology, Antineoplastic Agents pharmacology, Apoptosis drug effects, Citric Acid pharmacology, Ferric Compounds pharmacology, Lipid Peroxidation drug effects, Proto-Oncogenes, Sorbitol pharmacology
- Abstract
We described before that iron-containing, anti-anaemic drug, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of various murine cancer cells in vitro and caused tumour regression in vivo, but did not affect proliferation of the non-malignant cells. The aim of this study was to evaluate further the anticancer activity mechanism of FSC using human colon cancer cell line CaCo2. After treatment with FSC for 72 hours impaired proliferative ability and viability of CaCo2 cells as observed. Growth modification caused by FSC involved diminished expression of Bcl-2, and over-expression of mp53 proto-oncogenes, accompanied by increased incidence of apoptosis. Immunostaining the cells applying monoclonal antibodies for lipid peroxidation product 4-hydroxynonenal (HNE) showed that FSC-iron increased intracellular HNE, but did not induce severe HNE-mediated oxidative stress. Thus, antitumorous mechanism of FSC involves modulation of oncogene expression and induction of apoptosis apparently not triggered by lipid peroxidation-mediated oxidative stress, although FSC might restore endogenous HNE production in the CaCo2 cells to level resembling physiological for various non-malignant cells and tissues. Higher dose of FSC increased also number of intracellular ferritin positive CaCo2 cells.
- Published
- 2000
- Full Text
- View/download PDF
36. Transfer to in vitro conditions influences expression and intracellular distribution of galectin-3 in murine peritoneal macrophages.
- Author
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Dumić J, Lauc G, Hadzija M, and Flögel M
- Subjects
- Animals, Cells, Cultured, Galectin 3, Male, Mice, Mice, Inbred BALB C, Rats, Subcellular Fractions metabolism, Antigens, Differentiation metabolism, Macrophages, Peritoneal metabolism
- Abstract
Galectin-3 is a beta-galactoside-binding lectin that has been implicated in numerous physiological processes, including mRNA splicing, cell differentiation, tumor metastasis and the stress response. We have studied effects of transfer of resident murine peritoneal macrophages to in vitro conditions on galectin-3 in different cell compartments. Galectin-3 was purified by immunoprecipitation with rat monoclonal antibody M3/38, and analyzed by immunoblotting using the same antibody. Transfer to in vitro conditions nearly doubled the total amount of galectin-3 in cells, and caused significant alterations in its intracellular distribution, indicating that galectin-3 is involved in the adaptation of peritoneal macrophages to in vitro conditions.
- Published
- 2000
- Full Text
- View/download PDF
37. Inhibition of apoptosis is the cause of resistance to doxorubicin in human breast adenocarcinoma cells.
- Author
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Osmak M, Brozović A, Ambriović-Ristov A, Hadzija M, Pivcević B, and Smital T
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 analysis, DNA Fragmentation, Dose-Response Relationship, Drug, Drug Resistance, Multiple, Female, Glutathione analysis, Glutathione Transferase analysis, Humans, Neoplasm Proteins analysis, Tumor Cells, Cultured, Adenocarcinoma pathology, Antibiotics, Antineoplastic pharmacology, Apoptosis drug effects, Breast Neoplasms pathology, Doxorubicin pharmacology, Drug Resistance, Neoplasm
- Abstract
In our previous paper we have described the isolation and characterization of a doxorubicin (DOX) resistant subline of breast adenocarcinoma SC6 cells. These cells were obtained after the treatment with low, clinically relevant doses of doxorubicin. They became cross-resistant to different wide used cytostatics. The expression of several genes involved in mitotic signal transduction, as well as cathepsins D and L, was similar in both parental and doxorubicin treated cells. The aim of this study was to examine the molecular mechanisms involved in resistance of these cells to doxorubicin. Activity of plasma membrane Pgp was examined in parental and resistant cells due to rhodamine-accumulation assay. The involvement of glutathione (GSH) and glutathione S-transferase (GST) in resistance to doxorubicin was determined in MTT modified assay due to the addition of specific inhibitors: buthionine sulfoximine (for GSH) or ethacrynic acid (for GST). The kinetic of apoptosis was followed after the treatment with DOX in control and SC6 cells by fluorescent microscope. The occurrence of apoptosis was confirmed by analysing DNA fragmentation in agarose gel. Our results indicate that P-glycoprotein, glutathione or glutathione transferases were not involved in resistance of SC6 cells to doxorubicin. However, the apoptosis was inhibited in doxorubicin-resistant cells. Therefore, even low doses of doxorubicin can induce the resistance to this drug due to inhibition of apoptosis.
- Published
- 1998
38. Presence of c-Myc protein in murine myeloid leukaemia cells during growth and after irradiation.
- Author
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Popović-Hadzija M, Poljak-Blazi M, and Pavelić K
- Subjects
- Animals, Immunohistochemistry, Leukemia, Myeloid pathology, Leukemia, Myeloid radiotherapy, Mice, Leukemia, Myeloid metabolism, Proto-Oncogene Proteins c-myc analysis
- Abstract
Myeloid leukaemia (ML) is strain specific for RFM mice, which were used in these experiments. We investigated the presence of c-myc protein during the growth of ML and after irradiation of leukaemic cells. Leukaemic spleen cells were investigated 9 (nonterminal phase NTP) or 12 days (terminal phase TP) after the injection of ML cells. Leukaemic cells of NTP were irradiated with X-rays or UV-light. c-Myc protein was detected by immunocytochemical method. c-Myc protein was expressed in 74.98% of spleen cells of healthy RFM mice. In the early period of leukaemia growth (NTP) only 14.33% of c-myc positive cells were found, as opposed to the terminal phase (TP) of leukaemia when 89.7% of c-myc positive cells were detected. These results indicated the connection of growth of ML and the presence of c-myc protein. If the spleen cells of NTP of leukaemia were irradiated by X-rays or UV-light, the number of cells which expressed c-myc protein was extremely increased.
- Published
- 1997
39. Lipid bound sialic acid concentration in mice with myeloid leukemia and alloxan diabetes.
- Author
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Sverko V, Hadzija M, Gavella M, Lipovac V, Slijepcević M, and Radacić M
- Subjects
- Animals, Insulin pharmacology, Male, Methotrexate pharmacology, Mice, Mice, Inbred Strains, Diabetes Mellitus, Experimental metabolism, Leukemia, Myeloid metabolism, Lipid Metabolism, Sialic Acids metabolism
- Published
- 1993
- Full Text
- View/download PDF
40. Concentration of sialic acid in alloxan diabetic rat islets of Langerhans.
- Author
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Hadzija M, Lipovac V, Gavella M, Rocic B, and Slijepcevic M
- Subjects
- Animals, Cell Membrane metabolism, Male, N-Acetylneuraminic Acid, Neuraminidase metabolism, Neuraminidase pharmacology, Rats, Rats, Wistar, Time Factors, Diabetes Mellitus, Experimental metabolism, Islets of Langerhans metabolism, Sialic Acids metabolism
- Abstract
A microanalytical procedure for the determination of total and surface sialic acid concentrations was employed to establish their changes in relation to the length of alloxan diabetes in rat islets of Langerhans. 14 and 60 days after alloxan administration (65 mg/kg), the number of Langerhans islets was significantly decreased (p < 0.001) compared to the control. According to their size, the distribution of islets displayed no significant difference in diabetic and control animals 14 days after alloxan administration, while after 60 days no large islets (dia > or = 128 microns) were found in diabetic animals. The surface sialic acid was significantly increased in the small islets (p < 0.001), whereas no change was found in the large islets 14 days after alloxan administration. After 60 days, the surface sialic acid of both small and large islets was significantly decreased (p < 0.001). These results demonstrate that chronic beta-cell destruction induces a decrease in the sialic acid content in the pancreatic islet cells, suggesting that sialic acid might play a role in insulin secretory regulation regarding chronic effects of alloxan beta-cytotoxicity.
- Published
- 1992
41. Tryptophan content in serum and brain of long-term insulin-treated diabetic rats.
- Author
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Jamnicky B, Slijepcević M, Hadzija M, Juretić D, and Borcić O
- Subjects
- Amino Acids blood, Animals, Blood Glucose analysis, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental drug therapy, Male, Rats, Rats, Inbred F344, Reference Values, Tryptophan blood, Brain Chemistry, Diabetes Mellitus, Experimental metabolism, Insulin therapeutic use, Tryptophan analysis
- Abstract
The metabolism of tryptophan (TRP) was studied in diabetic and insulin-treated diabetic rats throughout a five-month period. In alloxan diabetic rats the serum and brain TRP levels were decreased (serum: 38 to 48 mmol/l, brain: 8.6 to 9.2 mmol/g) in comparison to the values of control rats (serum: 59 to 64 mmol/l, brain: 11.3 to 12.6 mmol/g). Daily long-term (for 45, 75, 90 or 135 days) treatment with intermediately acting insulin (4 IU/rat, s.c.) was not able to restore brain concentration of TRP. On the contrary, the serum TRP concentrations were totally or partially restored. The concentrations of branched chain amino acids (BCAA) were increased in serum (valine = 361.2 to 461.0 mumol/l or leucine + isoleucine = 431.0 to 520.3 mumol/l) throughout the entire five-month examination period. Insulin treatment did not return serum concentration of BCAA to normal level in the observation period either.
- Published
- 1991
- Full Text
- View/download PDF
42. Recovery of the immune system in diabetic mice after transplantation of isolated islets of Langerhans.
- Author
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Hadzija M, Slijepcević M, Sverko V, Marotti T, and Poljak-Blazi M
- Subjects
- Animals, Female, Immune System physiology, Islets of Langerhans immunology, Mice, Mice, Inbred C3H, Transplantation, Isogeneic, Diabetes Mellitus, Experimental immunology, Islets of Langerhans Transplantation
- Abstract
Adult CBA/HZgb mice islets harvested by collagenase digestion were injected intraperitoneally in 52 singeneic diabetic recipients (CBA/Hgb leads to CBA/HZgb, 450-600 islets per mouse). Normal serum glucose levels, 24-h urine volume, insulin levels and body weight were completely restored to normal in all recipients during the next 2-5 months. Immunological function was assessed in control, diabetic and diabetic-transplanted mice by following their responses to sheep erythrocytes (expressed as the number plaque-forming cells in the spleen). In transplanted mice, the plaque-forming cell responses were as follows: 1 month after transplantation--43% of the plaque-forming cell counts in control (normal, non-diabetic) mice; 2 months after transplantation--56% of the control value; and 94% of the control value after 5 months. Ten months after the transplantation, the plaque-forming cell counts were slightly above the control value (148%). It appears, therefore that transplantated islet tissue positively affects the immunological as well as the diabetic state of the recipients.
- Published
- 1984
- Full Text
- View/download PDF
43. Role of class I and class II antigens in specific immunosuppression after transfusion of UV-irradiated blood.
- Author
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Poljak-Blazi M and Hadzija M
- Subjects
- Animals, Graft vs Host Reaction, In Vitro Techniques, Mice, Mice, Inbred Strains, Ultraviolet Rays, Blood Transfusion, Erythrocytes radiation effects, H-2 Antigens immunology, Histocompatibility Antigens Class II immunology
- Published
- 1987
44. Erythrocyte sialic acid alterations in experimental diabetes.
- Author
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Gavella M, Lipovac V, Sverko V, and Hadzija M
- Subjects
- Animals, Body Weight drug effects, Erythrocytes drug effects, Female, Insulin pharmacology, Rats, Rats, Inbred Strains, Diabetes Mellitus, Experimental blood, Erythrocytes analysis, Sialic Acids blood
- Published
- 1985
45. [Separation of lymphocytes into classes from peripheral human blood using centrifugation on a discontinuous gradient].
- Author
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Hadzija M, Poljak-Blazi M, and Boranić M
- Subjects
- Humans, Lymphocyte Activation, Phytohemagglutinins pharmacology, Rosette Formation, B-Lymphocytes, Cell Separation methods, Centrifugation, Density Gradient, T-Lymphocytes
- Abstract
Peripheral blood lymphocytes of 20 normal volunteers were separated on a discontinuous gradient of Ficoll. The ability of lymphocytes from the fractions to from sponteneous (E) and induced (EAC) rosettes and undergo transformation in the presence of phytohaemagglutinin (PHA) was tested. T-lymphocytes were concentrated in the density of 1,067 g/ml and B-lymphocytes in the density of 1,063 g/ml.
- Published
- 1978
46. Suppression of donor lymphocyte reactivity by pretreatment with recipient type UV-irradiated blood.
- Author
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Polijak-Blazi M and Hadzija M
- Subjects
- Animals, Bone Marrow radiation effects, Hematopoietic Stem Cells radiation effects, Immunization, Passive, Lymphocyte Transfusion, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Transplantation, Homologous, X-Rays, Blood Transfusion, Bone Marrow Transplantation immunology, Immune Tolerance radiation effects, Immunosuppression Therapy methods, Ultraviolet Rays
- Published
- 1987
47. Effect of the degree of hyperglycaemia on the catalytic activities of glycosidases in kidney and urine of diabetic rats.
- Author
-
Juretić D, Lipovac K, Hadzija M, and Slijepcević M
- Subjects
- Animals, Blood Glucose metabolism, Diabetes Mellitus, Experimental pathology, Female, Glycoside Hydrolases urine, Insulin therapeutic use, Kidney pathology, Rats, Rats, Inbred Strains, Time Factors, Diabetes Mellitus, Experimental enzymology, Glycoside Hydrolases metabolism, Hyperglycemia enzymology, Kidney enzymology
- Abstract
The catalytic activities of N-acetyl-beta-D-glucosaminidase, beta-galactosidase and alpha-glucosidase in kidney and urine of diabetic rats were investigated in relation to the duration of diabetes, to the degree of constant hyperglycaemia and to the therapeutic control in the early stage of disease. The results suggest that the degree of constant hyperglycaemia and the duration of untreated diabetes are significant determining factors for the course of morphological changes. These changes are manifested as a decrease of the glycosidases in kidney (0.5 to 0.6 time the age-matched controls) and as moderate to severe enzymurias. Daily variation of blood glucose with inadequate insulin Lente therapy caused decreased N-acetyl-beta-D-glucosaminidase and beta-galactosidase activities in kidney as well as enzymuria. Since such changes can be correlated with histologically visible changes in the kidney, the measurement of these enzymes in urine is a simple way of monitoring the development of kidney damage in poorly controlled diabetes. When constant normoglycaemia was maintained for three weeks with insulin Ultralente in diabetic rats with a confirmed decrease of kidney glycosidases, the persisting morphological alteration of the organ was reflected by a urinary output of N-acetyl-beta-D-glucosaminidase.
- Published
- 1984
- Full Text
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