Mirko Spiroski
Professor of immunology and human genetics.
Research skills
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TechnicalSSP, SBT, RLS, Immunonephelometry, ImmmunoCap
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ITWeb Design
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StatisticalPyPop, Arlequin, Statgraph
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OtherMedical Writing, Journal Editing
Research interests
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InterestsHuman Genetics
Research experience
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Teaching: Immunology
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Teaching: human genetics
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Teaching: Public genetics
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Teaching: Genetics in sport
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Teaching: Immunochemistry
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Teaching: Molecular biology of the gene (Biochemistry-3
Other
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LanguagesEnglish, Macedonian (mother), Serbian
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Other InterestsMusic., http://www.mjms.ukim.edu.mk/
Publications
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2.55Impact points
IL10 -1082, IL10 -819 and IL10 -592 polymorphisms are associated with chronic periodontitis in a Macedonian population.
Human immunology. 04/2012;
Genetic polymorphisms in the interleukin 10 (IL10) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL10 gene and its relation with periodontal disease in a Mace... [more] Genetic polymorphisms in the interleukin 10 (IL10) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL10 gene and its relation with periodontal disease in a Macedonian population. The study population consisted of 111 unrelated subjects with chronic periodontitis and 299 healthy controls. DNA was isolated and IL10 genotyping performed by PCR-SSP (Heidelberg kit) for the alleles and genotypes of IL10 -1082, IL10 -819 and IL10 -592. Frequencies of IL10 haplotypes and the haplotype zygotes were also examined. Comparisons between groups were tested using the Pearson's p-value. After Bonferroni adjustment, significant associations were detected between subjects with chronic periodontitis and IL10 genotypes (IL10 -1082/A:G was negative or protective and IL10 -1082/G:G was positive or susceptible). Cytokine polymorphism on the IL10 gene appears to be associated with susceptibility to chronic periodontitis in Macedonians.
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0.97Impact points
Gene polymorphisms of 22 cytokines in macedonian children with atopic dermatitis.
Iranian journal of allergy, asthma, and immunology. 03/2012; 11(1):37-50.
Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with abnormal cytokine production, and activation of T-helper 2 cells. The aim if this study was to determine whether cytokine gene polymorphisms might influence the development of AD. Single nucleotide polymorphisms in... [more] Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with abnormal cytokine production, and activation of T-helper 2 cells. The aim if this study was to determine whether cytokine gene polymorphisms might influence the development of AD. Single nucleotide polymorphisms in the genes for I-L1alpha, IL-1beta, IL-1R, IL-2, IL-4, IL-6, IL-10, IL-12, TGF beta, TNF and IFNgamma were investigated by PCR and sequence specific primers in Macedonian patients with AD (67 children, age of 6 months to 5 years) and 301 normal unrelated individuals. Susceptible cytokine polymorphisms for AD for eleven genotypes (IL-4 -33/T:T IL-4 -1098/G:G, TGFbeta cdn25C:G, IL-4 -1098/T:T, IL-1alpha -889/C:T, IL-2 +166/T:T, IL-1beta -511/C:T, IL-12 -1188/C:T, IL-10 -1082/A:G, IL-1beta +3962/C:T, IFNgamma +874/A:T), five diplotypes, six haplotypes, and for alleles were found. Protective cytokine polymorphisms for AD for seven cytokine genotypes (IL-4 -1098/G:T, TGFbeta cdn25/G:G, IL-4 -33/C:C, IL-1alpha -889/C:C, IFNgamma +874/A:A, IL-10 -1082/A:A, IL-1beta -511/C:C), one cytokine diplotypes, two cytokine haplotypes, and four cytokine alleles were also found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with AD in population of Macedonians.
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0.32Impact points
Low density lipoprotein size in relation to carotid intima-media thickness in coronary artery disease.
Bratislavské lekárske listy. 01/2012; 113(2):87-91.
Objective: With increasing interest in the role of non-traditional lipid risk factors in coronary artery disease, we undertook this study to relate LDL subclass size and carotid intima-media thickness of the common carotid artery in coronary artery disease patients.Methods: The study was conducted i... [more] Objective: With increasing interest in the role of non-traditional lipid risk factors in coronary artery disease, we undertook this study to relate LDL subclass size and carotid intima-media thickness of the common carotid artery in coronary artery disease patients.Methods: The study was conducted in 106 patients during their first visit (study group I) and after 12 months (study group II). Intima-media thickness of the common carotid artery was determined using B-mode ultrasound. Separation of LDL subclasses was preformed by 3-31 % polyacrylamide gradient gel electrophoresis. Results: LDL3 was the dominant subclass in both study groups, but there was statistically significant difference in the distribution of dominant LDL subclasses (p<0.01). The mean carotid intima- media thickness was significantly increased (p<0.001) in coronary artery disease patients after 12 months period. There was significant negative correlation between intima-media thickness and LDL size in both study groups (p<0.05). Intima-media thickness was not significantly correlated with plasma lipid concentrations. Multiple regression analyses show that strongest independent predictor of the intima-media thickness variation was diastolic blood pressure, followed by LDL size and age, and accounted for 29 % of the observed variability in intima-media thickness.Conclusion: LDL particle size is independently associated with carotid intima-media thickness in coronary artery disease patients with normal levels of traditional lipid risk. These results imply that small, dense LDL subclasses are an important indicator for assessing atherosclerosis and its progression (Tab. 4, Ref. 39). Keywords: LDL size, gradient gel electrophoresis, intima-media thickness, CAD.
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1.52Impact points
Distribution of killer cell immunoglobulin-like receptor genes in Roma from Republic of Macedonia.
International journal of immunogenetics. 09/2011; 38(6):493-500.
The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene polymorphisms in Roma people from Republic of Macedonia. The studied sample consists of 103 healthy unrelated individuals, aged 20-45 years. All individuals are of Roma origin, residents of different geographical regions (Gostiv... [more] The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene polymorphisms in Roma people from Republic of Macedonia. The studied sample consists of 103 healthy unrelated individuals, aged 20-45 years. All individuals are of Roma origin, residents of different geographical regions (Gostivar, Skopje, and Kochani). The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the Roma individuals and framework genes (KIR3DL3, KIR3DP1, KIR- 2DL4, and KIR3DL2) were present in all individuals. The frequencies of other KIR genes were: KIR2DP1 (1), KIR2DL1 (0.961), KIR2DL2 (0.544), KIR2DL3 (0.874), KIR2DL5 (0.311), KIR3DL1 (0.990), KIR- 2DS1 (0.330), KIR2DS2 (0.553), KIR2DS3 (0.359), KIR2DS4 (0.981), KIR2DS5 (0.291), and KIR3DS1 (0.379). The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. The obtained results for KIR genes and genotype frequencies in Macedonian Roma individuals can be used for anthropological comparisons.
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2.55Impact points
IL4 gene polymorphisms and their relation to periodontal disease in a Macedonian population.
Human immunology. 02/2011; 72(5):446-50.
Genetic polymorphisms in the interleukin-4 (IL4) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL4 gene and its relation with periodontal disease in a Macedon... [more] Genetic polymorphisms in the interleukin-4 (IL4) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL4 gene and its relation with periodontal disease in a Macedonian population. The study population consisted of 92 unrelated subjects with chronic periodontitis and 286 healthy controls. DNA was isolated and IL4 genotyping performed by polymerase chain reaction-single-strand polymorphism (Heidelberg kit) for the alleles and genotypes of IL4 -1098, IL4 -590, and IL4 -33. Frequencies of IL4 haplotypes and the haplotype zygotes were also examined. Comparisons between groups were tested using the Pearson's p value. After Bonferroni adjustment, significant associations were detected between subjects with periodontitis and the following: (1) cytokine alleles IL4 -1098 and IL4 -33; (2) cytokine genotypes IL4 -1098/G:T; IL4 -1098/T:T, and IL4 -33/T:T, (3) cytokine haplotypes IL4/GCC, IL4/TCC, and IL4/TTC; and (4) cytokine haplotype zygotes IL4/TTC: TCC, IL4/TCT:TTT, and IL4/GCC:TTC. Cytokine polymorphism on the IL4 gene appears to be associated with susceptibility to chronic periodontitis in Macedonians.
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Hyper IgE in a HIV Positive Patient - Case Report
Macedonian Journal of Medical Sciences. 01/2011;
Background: Hyperimmunoglobulinemia E Syndrome (HIES) is a primary immunodeficiency syndrome associated with multiple abnormalities. Clinical manifestations of atopic allergy, drug reactions, and increased IgE in serum were previously reported during the course of human immunodeficiency virus (HIV) ... [more] Background: Hyperimmunoglobulinemia E Syndrome (HIES) is a primary immunodeficiency syndrome associated with multiple abnormalities. Clinical manifestations of atopic allergy, drug reactions, and increased IgE in serum were previously reported during the course of human immunodeficiency virus (HIV) infection. Case report: We herby describe the case of one 63 yrs old male patient with a history of weight loss and diarrhoea, who was previously treated for enterocolitis. He was also treated at the Dermatological Clinic for herpes zoster infection and undiagnosed allergy. Microbiology tests showed presence of Candida and Klebsiella pneumoniae in the patient’s sputum which led to testing and confirmation of HIV/AIDS. After that, Lues was diagnosed and blood sample was sent to our laboratory, to evaluate if this atopic patients was sensitized to beta-lactam antibiotics. The results showed increased level of total IgE for almost 12 times above normal ranges and also allergy to ampicillin was revealed. Highly increased levels of total IgE indicated the possibility for HIE Syndrome in this patient. However the relationship of such findings to the immunologic abnormalities found in patients with HIV is not entirely clear. Conclusion: In conclusion, this is the first case of HIV positive patient with hyper IgE immunoglobulinemia in the Republic of Macedonia. We addressed the important laboratory findings and actual theories explaining possible association between hyper IgE immunoglobulinemia and HIV/AIDS.
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A case report of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome.
Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences. 07/2010; 31(1):349-59.
(Full text is available at http://www.manu.edu.mk/prilozi). A case of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome is described. Pancytopenia and circulating blasts cells at presentation suggested the diagnosis of acute leukemia in the previously he... [more] (Full text is available at http://www.manu.edu.mk/prilozi). A case of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome is described. Pancytopenia and circulating blasts cells at presentation suggested the diagnosis of acute leukemia in the previously healthy 38 years old Caucasian male patient, but flow-cytometry analysis of the bone marrow disclosed the correct diagnosis of neuroblastoma. The immunophenotype was CD45-/CD56+/CD9+ in around 50% of the mononuclear cells, indicating neuroectodermal origin of the malignant cells. Subsequently, the diagnosis was confirmed by immunohistochemical staining of a bone marrow biopsy. A review of the reported cases of neuroblastoma with leukemic features showed that several of them were misdiagnosed as having leukemia and that the diagnosis of neuroblastoma was made at autopsy examination, indicating that misdiagnosis may happen more often than is appreciated. It is in our opinion that the diagnosis of neuroblastoma should be considered in all cases of acute leukemia and pancytopenia, regardless of the age group of the patients. Key words: neuroblastoma; immunophenotype; acute leukemia; CD56.
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2.33Impact points
Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report).
Tissue antigens. 03/2010; 76(1):18-30.
During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from pre... [more] During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.
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Letter to the Editor on “Erythropoietin production in patients with malignant lymphoma”, Kostova G, Siljanovski N. Prilozi. 2005;26(2):157-68.
Macedonian Journal of Medical Sciences. 01/2010;
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Country Rank, Journal Rank and H-Index in the Field of Medicine in the Republic of Macedonia (1996-2008) Using Data from SCImago
Macedonian Journal of Medical Sciences. 01/2010;
Aim. The aim of this study was to present the country rank, journal rank and H-index in the field of medicine in the Republic of Macedonia (1996-2008) using data from SCImago Journal & Country Rank (SCImago).Material and Methods. SCImago database was used for analysis of country rank, journal ra... [more] Aim. The aim of this study was to present the country rank, journal rank and H-index in the field of medicine in the Republic of Macedonia (1996-2008) using data from SCImago Journal & Country Rank (SCImago).Material and Methods. SCImago database was used for analysis of country rank, journal rank and H-index in the Republic of Macedonia and other former Yugoslav countries (Slovenia, Croatia, Serbia, Bosnia and Herzegovina, and Montenegro) for the period of 1996-2008, as they are presented in the Scopus database.Results. Of a total number of 222 countries for the period of 1996-2008, the Republic of Macedonia with H-index of 20 is placed on the 118th position of the country rank, the percentage of citable documents in the field of medicine is 88.92%, and the percentage of relative production of documents in the world is below 0.01. In 2008, Macedonian biomedical journal Prilozi is ranked on the 2484th place with 0.048 SJR of citable documents in the last three years. The biggest H-index of 10, for the period between 2007and 2008, in the Republic of Macedonia had nephrology subject category, followed by medicine (miscellaneous) with H-index of 7, haematology and endocrinology, diabetes and metabolism with H-index of 6, transplantation, oncology and pathology and forensic medicine with H-index of 5.Conclusion. There is only one Macedonian biomedical journal (Prilozi, Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences) included in the Scopus database for the period between 1996 and 2008, probably by mistake in the list of journals from Serbia, instead from the Republic of Macedonia. The priority task of the Editorial Boards of other Macedonian medical journals is to include their journals in the Scopus database.
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Bgl II Polymorhism of the alpha2beta1 Integrin Gene in Macedonian Population
Macedonian Journal of Medical Sciences. 01/2010;
Background. Glycoprotein (GP) Ia/IIa or a2b1 integrin is a platelet receptor for collagen and it mediates platelet adhesion to vascular subendothelium and is involved in thromb formation. Genetic polymorphism of alpha2beta1 known as Bgl II affects the density of platelet GP Ia/IIa receptor on the pl... [more] Background. Glycoprotein (GP) Ia/IIa or a2b1 integrin is a platelet receptor for collagen and it mediates platelet adhesion to vascular subendothelium and is involved in thromb formation. Genetic polymorphism of alpha2beta1 known as Bgl II affects the density of platelet GP Ia/IIa receptor on the platelet surface. Recent studies had shown relationship between this polymorphism and the risk of myocardial infarction, stroke, as well as diabetic retinopathy. Aim. The aim of this study was to determine the frequency of this polymorphism in Macedonian healthy population. Materials and Methods. We genotyped 217 healthy Macedonian individuals using the PCR and RFLP (restriction fragment length polymorphism) method.Results. The allele frequencies in this study were 0.32 for Bgl II (+) allele and 0.67 for Bgl II (-). Distribution of Bgl II genotypes in Macedonian population was Bgl II (+/+) = 16/217 (7.3%), Bgl II (+/-) =107/217 (49.3%) and Bgl II (-/-) = 94/217 (43.3%). Conclusion. Our results showed a slightly lower proportion of the Bgl II (+) allele (0.32) in Macedonian population, but not significantly different from other Caucasian population.
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Qualitative Histological Analysis of Adrenal Cortex Following Application of Medroxyprogesterone Acetate
Macedonian Journal of Medical Sciences. 01/2010;
Aim. The aim of the investigation was to make a review of the morphological characteristics of the adrenal cortex following the application of high doses of medroxyprogesterone acetate (MPA). Material and Methods. Total of 48 female Wistar rats were divided into four groups. Control group was given... [more] Aim. The aim of the investigation was to make a review of the morphological characteristics of the adrenal cortex following the application of high doses of medroxyprogesterone acetate (MPA). Material and Methods. Total of 48 female Wistar rats were divided into four groups. Control group was given saline daily, intramuscularly, and the other three groups MPA in doses of 7.5, 15.0 and 75.0 mg/kg bw during 30 days. Paraffin sections from adrenal glands were stained according the following methods: hematoxylin-eosin, Azan modified by Heidenhein, Van-Gieson, Kossa-Goldner, Masson and Florentin. Results. Histological analysis demonstrated that MPA caused the following morphological changes in adrenal cortex: more intensive development of stroma; decrease of adrenal cortex thickness; disturbance of spacial organization of adrenocorticocytes in glomerular zone, fascicular zone and reticular zone; atrophic changes of adrenocorticocytes; disappearance of intermediary zone after application of 75.0 mg/kg bw MPA; appearance of microcysts in fascicular and reticular zones; decrease of cortical proliferate dimensions and accessory adrenal glands, disappearance of spongiocytes from their structure and atrophic changes of glomerular cells; decrease of adrenal cortex vascularisation, necrotic changes localized subglomerularly and in fascicular zone of adrenal cortex. Conclusion. MPA causes atrophic changes in adrenal cortex i.e., the decrease of its cell potential, a phenomenon suggesting that MPA possesses glucocorticoid characteristic.
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Retraction: Ana Strezova. Genotyping of HLA-A, HLA-C and HLA-B Loci with Reverse Line Strip Hybridization in Macedonian Population and Association of HLA Class I Alleles with Spondilitis [MSc thesis]
Macedonian Journal of Medical Sciences. 01/2010;
Aim. The aim of this report is to retract the results of Ana Strezova submitted without permission of her mentor and her institution for Master of Science (MSc) degree at the Faculty of Medicine, University “Ss Cyril and Methodius”, Skopje, Republic of Macedonia.Material and Methods. Two populations... [more] Aim. The aim of this report is to retract the results of Ana Strezova submitted without permission of her mentor and her institution for Master of Science (MSc) degree at the Faculty of Medicine, University “Ss Cyril and Methodius”, Skopje, Republic of Macedonia.Material and Methods. Two populations were published from the same cohort: i) in the 15th International Histocompatibility and Immunogenetics Workshop 250 samples for HLA-A, 247 samples for HLA-B, 250 samples for HLA-C, 564 samples for HLA-DRB1, and 213 samples for HLA-DQB1 were included; and ii) in retracted MSc degree 250 samples for HLA-A, HLA-B and HLA-C were included. Results. HLA DNA typing results from Macedonian population were officially submitted for analysis and publication to the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS). Results were prepared and submitted for publication in Tissue Antigens (received 7 July 2009; revised 12 January 2010; accepted 1 February 2010). Ana Strezova without permission of her mentor and director of the Institute of Immunobiology and Human Genetics submitted MSc thesis for defence with the identical results as in submitted manuscript. A total number of 5 HLA genes and 220 alleles are published by the 15th International Histocompatibility and Immunogenetics Workshop in comparison with 3 HLA genes and 58 alleles in retracted MSc thesis. Conclusion. The results of the MSc thesis of Ana Strezova with the title “Genotyping of HLA-A, HLA-C and HLA-B Loci with Reverse Line Strip Hybridization in Macedonian Population and Association of HLA Class I Alleles with Spondilitis” are retracted because: i) the content was already submitted for publication; ii) the statistical methods are inappropriate for ambiguous resolution of the data; and iii) the permission was not allowed by her mentor and director. Editors-in-Chief and employers are advised to be aware of possible acceptance of this thesis and the results submitted in the future for publication.
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Quantitative Analysis of Adrenal Cortical Histological Alterations After Application of Medroxyprogesterone Acetate
Macedonian Journal of Medical Sciences. 01/2010;
Aim. The aim of our investigation was to make a quantification of the changes being registered by a quantitative histological analysis of adrenal cortex after long-term application of high doses of medroxyprogesterone acetate (MPA). Material and Methods. A total of 48 female Wistar rats were divided... [more] Aim. The aim of our investigation was to make a quantification of the changes being registered by a quantitative histological analysis of adrenal cortex after long-term application of high doses of medroxyprogesterone acetate (MPA). Material and Methods. A total of 48 female Wistar rats were divided into four groups. The control group was given saline intramusculary, every day, and the other three groups MPA in doses of 7.5, 15.0 and 75.0 mg/kg bw, respectively, during 30 days. Paraffin sections from adrenal glands were stained according the following methods: hematoxylin-eosin, Azan, modified by Heidenhein, and Masson. Results. Gravimetric and variance analysis demonstrated the most remarkable decrease of the adrenal gland weight after the application of 75.0 mg/kg/bw MPA (from 35.66 ± 11.78 to 13.41 ± 8.41 mg (p<0.001). On the other hand, morphometric analysis demonstrated that adrenal cortex volume was the most significantly reduced from 11.30 ± 3.53 in the control group to 2.04 ± 0.90 mm3 in the group treated with 15.0 mg/kg bw MPA (p<0.0001). Adrenal cortex thickness was reduced from 846.06 ± 6.48 to 349.55 ± 4.84 mcm after the application of 75.0 mg/kg bw (p < 0.001). After the application of the same dose the glomerular zone thickness was decreased from 48.02 ± 0.44 to 41.40 ± 0.43 mcm (p < 0.001), the fascicular zone thickness from 480.72 ± 3.43 to 194.32 ± 2.80 mcm (p <0.001) and the reticular zone thicknes reduced from 317.47 ± 4.80 to 113.85 ± 2.28 mcm (p < 0.001). The volume of glomerular zone cell nuclei decreased most remarkably from 94.79 ± 0.96 mcm3 after the application of 75.0 mg/kg bw to 60.12 ± 0.88 mcm3 (p < 0.001). The volume of fascicular zone cell nuceli decreased from 166.30 ± 1.53 to 52.47 ± 0.89 mcm3 (p < 0.001), while the volume of reticular zone cell nuceli reduced from 95.61 ± 1.03 to 47.68 ± 0.92 mcm3 (p < 0.001). The analysis by means of c2 test showed that the appearance of tissue necrotic changes in adrenal cortex had a statistical significance only after the application of the highest dose of MPA (p < 0.012). Conclusion. The quantitative histological analysis showed significant decrease of the adrenal cortex, i.e. decrease of glomerular, fascicular and reticular zone thickness and significant decrease of the adrenocorticocytes nuclei volume, changes which suggested that MPA caused an atrophy of the adrenal cortex.
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2.55Impact points
Distribution of Killer Cell Immunoglobulin-Like Receptors in the Macedonian Population.
Human immunology. 12/2009;
The aim of this study was to analyze Killer Ig-Like Receptor (KIR) Gene Polymorphism in the Macedonian Population. The studied sample consists of 214 healthy unrelated individuals, aged 20-35 years. All individuals are of Macedonian origin and nationality, residents of different geographical regions... [more] The aim of this study was to analyze Killer Ig-Like Receptor (KIR) Gene Polymorphism in the Macedonian Population. The studied sample consists of 214 healthy unrelated individuals, aged 20-35 years. All individuals are of Macedonian origin and nationality, residents of different geographical regions. The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the Macedonian population and framework genes KIR3DL3, KIR2DL4,and KIR3DL2were present in all individuals. Total of 56 different KIR genotypes were found to be present in Macedonian population, based on the presence of 16 KIR genes. Neighbor-Joining phylogenetic tree, constructed on the basis of standard genetic distances of KIR genes, shows that Macedonian population is in the same cluster with England West Midlands Indian Asian, Brazil South East Caucasian, Romania Caucasians, Spain Basque, England West Midlands Caucasian, France Reunion, and Spain Granada populations. The frequency of KIR loci in Macedonian population shares several general features with other Caucasoid populations studied before.
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0.25Impact points
Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.
Bosnian journal of basic medical sciences / Udruženje basičnih mediciniskih znanosti = Association of Basic Medical Sciences. 11/2009; 9(4):283-9.
Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the i... [more] Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.
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0.57Impact points
Association between 22 cytokine gene polymorphisms and dilated cardiomyopathy in Macedonian patients.
Kardiologia polska. 11/2009; 67(11):1237-1247.
Background: Inflammation is an important component in the pathogenesis of many cardiovascular diseases and one of the commonest mechanisms in cardiomyopathy. There have been several studies on the cytokine polymorphism and dilated cardiomyopathy (DCM), but the results obtained were contradictory. Ai... [more] Background: Inflammation is an important component in the pathogenesis of many cardiovascular diseases and one of the commonest mechanisms in cardiomyopathy. There have been several studies on the cytokine polymorphism and dilated cardiomyopathy (DCM), but the results obtained were contradictory. Aim: To examine a possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against DCM in Macedonians. Methods: In this study 301 healthy unrelated individuals and 52 patients with DCM were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). Results: After the Bonferroni adjustment, the IL-4 -1098/T, IL-4 -1098/T:T, IL-4/TCC, and IL-4/TCC:TTC cytokine genes were positively associated with DCM, while a negative association was identified for IL-4 -1098/G, IL-4 -1098/G:T, IL-1B +3962/C:C, IL-4/GCC, and IL-4/GCC:TTC. Conclusions: These results suggest that some cytokine gene polymorphisms are significantly associated and affect host susceptibility/resistance to DCM in Macedonians.
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0.57Impact points
Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis.
Kardiologia polska. 10/2009; 67(10):1088-1094.
Background: Raised SERPINE1 plasma levels are related to a 1-bp guanine deletion/insertion (4G5G) polymorphism in the promoter of the SERPINE1 (plasminogen activator inhibitor 1 - PAI1) gene. Evidence suggested that the plasma levels of SERPINE1 modulate the risk of coronary artery disease; furtherm... [more] Background: Raised SERPINE1 plasma levels are related to a 1-bp guanine deletion/insertion (4G5G) polymorphism in the promoter of the SERPINE1 (plasminogen activator inhibitor 1 - PAI1) gene. Evidence suggested that the plasma levels of SERPINE1 modulate the risk of coronary artery disease; furthermore, that the 4G5G polymorphism affects the expression of the SERPINE1 gene. Aim: To analyse association of SERPINE1 polymorphism with occlusive artery disease (OAD) and deep venous thrombosis (DVT) in Macedonians in order to investigate its role as a part of candidate genes in different vascular diseases in Macedonians. Methods: Investigated groups consisted of 82 healthy patients, 75 with OAD, and 66 with DVT. Blood samples were collected after written informed consent was obtained, and DNA was isolated from peripheral blood leukocytes. Identification of SERPINE1 polymorphism was done with CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). The population genetics analysis package, PyPop, was used for analysis of the SERPINE1 data. Pearson's P-values, crude odds ratio and Wald's 95% CI were calculated with Bonferroni corrected p value. Results: The frequency of 4G allele for SERPINE1 was 0.538 for DVT, 0.555 for healthy participants, and 0.607 for OAD. The frequency of 5G allele for SERPINE1 was the smallest in patients with OAD (0.393) and was higher in healthy participants (0.445), and patients with DVT (0.462). Test of neutrality (Fnd) showed negative value, but was significantly different from 0 for SERPINE1 in healthy participants (p of F = 0.041) and in patients with DVT (p of F = 0.030). SERPINE1 genotypes in healthy participants and patients with OAD were not in Hardy Weinberg proportions (p = 0.019 and 0.001, respectively). No association between SERPINE1 polymorphisms and OAD or DVT was found. Conclusion: There is no significant relationship between SERPINE1 polymorphisms and occlusive artery disease or deep venous thrombosis in Macedonian population.
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1.67Impact points
Association of 22 cytokine gene polymorphisms with rheumatoid arthritis in population of ethnic Macedonians.
Clinical rheumatology. 09/2009;
To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against RA in Macedonians. In this study, 301 healthy unrelated individuals and 85 patients with RA were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (... [more] To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against RA in Macedonians. In this study, 301 healthy unrelated individuals and 85 patients with RA were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). Results showed susceptible association for four cytokine alleles, six cytokine genotypes, one haplotype, and four combinations of haplotypes, while protective associations were found for four cytokine alleles, three cytokine genotypes, three haplotypes, and only one combination of haplotypes. These results suggest that IL-4 -1098, IL-4 -590, IL-10 -1082, IL-10 -819, IL-2 -330, IL-6 -174, and TNF-alpha -238 cytokine gene polymorphisms might be significantly associated and affect host susceptibility and/or resistance to RA in Macedonians.
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Association of 22 cytokine gene polymorphisms with tuberculosis in Macedonians.
The Indian journal of tuberculosis. 07/2009; 56(3):117-31.
To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against tuberculosis (TB) in Macedonians. 301 healthy unrelated individuals and 75 patients with pulmonary TB were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (... [more] To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against tuberculosis (TB) in Macedonians. 301 healthy unrelated individuals and 75 patients with pulmonary TB were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). TNF-alpha-238/G, IL-1R psti1970/C, IL-1beta + 3962/T:T, IL-4-1098/T:T, IFNgamma utr5644/A:A, IL-10-1082/G:G, IL-4-590/C:C, IL-10/ATC, IL-4/TCT, IL-4/TCC, IL-10/ATC:GCC, IL-4/TCT:TTT, IL-4/TCC:TTC, IL-10/GCC:GCC and IL-4/TCC:TCC were positively associated with TB, while protective association was identified for IL-4-098/G, IL-1beta + 3962/C, IFNgamma utr5644/T, IL-1beta + 3962/C:T, IL-4-1098/G:T, IL-4-590/C:T, IFNgamma utr5644/A:T, IL-4/GCC, IL-4/TTC and IL-4/GCC:TTC. These results suggest that some cytokine polymorphisms are significantly associated and affect host susceptibility/resistance to TB in Macedonians.
Following (11)
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Dr.Abdul Wahab
University of Kent -
Vladimir E Trajkovski
Faculty of Philosophy -
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Deepak Mishra
Reseapro Scientific Services Pvt. Ltd. -
Anita Kloss-Brandstätter
Medizinische Universität Innsbruck
