Showing papers by "Mariusz Kaczmarczyk published in 2009"

Experience With Autosomal Dominant Polycystic Kidney Disease in Patients Before and After Renal Transplantation: A 7-Year Observation

Abstract: Objective Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of multiple cysts in both kidneys. Symptoms of the disease may arise either from the presence of cysts or from increasing loss of kidney function. First symptoms usually appear in the third decade of life: lumbar pain, urinary tract infections, arterial hypertension, or renal colic due to cyst rupture or coexistent nephrolithiasis. An early diagnosis, male gender, large kidneys by sonography, arterial hypertension, hematuria, and urinary tract infections are predictive factors of a faster progression of the disease. Our aim was to establish the indications for nephrectomy among symptomatic ADPKD patients before kidney transplantation and to assess the risks of posttransplantation complications among ADPKD patients without nephrectomy. Patients and Methods The observed group consisted of 183 patients with ADPKD among whom 50 (27.3%) underwent kidney transplantation during a 7-year observation period (2000–2007). Among those subjects were 3 groups: (I) nephrectomy preceding transplantation; (II) nephrectomy during kidney transplantation; and (III) without nephrectomy. Results Among group I before transplantation we observed: arterial hemorrhage, wound infections, and splenectomy 4 weeks after ADPKD nephrectomy; afterward we observed: urinary tract infections and contralateral cyst infection. Among group II we only observed 1 case of wound infection. Among group III we observed: ascending urinary tract infections, cyst infections, and cyst hemorrhage. Cyst hemorrhage and cyst infections led mainly to ADPKD kidney nephrectomy. During the observation time, 80.95% of grafts were functioning. Conclusions Unilateral nephrectomy is a well-founded preliminary surgical treatment before kidney transplantation. Bilateral nephrectomy before or during transplantation eliminates ADPKD complications and does not significantly increase general complications. The greatest numbers of complications and of graft losses were observed among the group without pretransplantation nephrectomy.

Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages.

Abstract: Conjugated linoleic acid (CLAs) are positional and geometric isomers of linoleic acid with have a potential anti-atherosclerotic and anti-inflammation properties. Metabolites of arachidonic acid--prostaglandins and thromboxans--are endogenous mediators of inflammation. Prostaglandin E(2) and thromboxan A(2) which are a products of two izoformes of cyclooxygenases (COX-1 and COX-2) in macrophages, play an important role in this process. COX-1 is a constitutive enzyme, whereas the COX-2 is inducible and its amount in the cell rapidly increases during inflammation (e.g. via NF kappaB pathway). The aim of the study was to test the effect of CLAs on cyclooxygenases (COX-1 and COX-2) activity, their mRNA expression and protein content in macrophages. Additionally the active form of the kappaB (NF kappaB) transcription factor was measured. For the experiments monocytes from monocytic cell line (THP-1) and from human venous blood were used. Monocytes were differentiated to macrophages and cultured with 30 muM CLAs or linoleic acid for 48 h. The COX-1 and COX-2 products - PGE(2) and TXB(2), were measured by ELISA method. The enzymes (COX-s) activity were estimated by spectroscopic method. mRNA expression and protein analysis were analysed by real-time PCR and Western blot technique. In macrophages cultured with CLAs reduction of TXB(2) and PGE(2) concentration was observed. Significant change in COX-2 expression in cells cultured with trans-10, cis-12 CLA (in macrophages obtained from peripheral blood) was observed. COX-1 inhibition was resulting from competition of CLA and linoleic acid with arachidonic acid.

C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects.

Abstract: Hyperhomocysteinemia is reported to be an independent risk factor for the development of ischemic stroke. Several studies on genetic variants of methylenetetrahydrofolate reductase (MTHFR, which plays a crucial role in regulation of plasma homocysteine concentration) reported an association between C677T gene polymorphism and stroke in some Asian populations. No study but one detected this association in Caucasians. The purpose of the present case-control study was to find a relationship betweenMTHFR genotypes and stroke in a Polish population.MTHFR genotypes were determined by PCR in 152 patients with ischemic stroke from northwestern Poland and in 135 consecutive newborns from the same population. The TT genotype and the T allele were significantly more frequent in patients than in the control group (11.8% vs. 4.4%, and 34.5% vs. 21.5%,P < 0.01). When males and females were analyzed separately, the differences were statistically significant in both genders. It is concluded that presence of the T allele is a risk factor for ischemic stroke in Polish subjects.

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.

Abstract: Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Δ32CCR5, G(-2459)ACCR5, G190ACCR2, G744ACX3CR1 and C838TCX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for A32CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for theCCR5 polymorphisms, with the A32 allele and the (-2459)ACCR5 allele more frequent among neonates than in the HIV(+) group. No Δ32/Δ32 homozygotes were found in the HIV(+) group, but 16.1% were Δ32/wt heterozygotes. In the control group, 1.3% were Δ32/Δ32 homozygotes and 26.0% were Δ32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Δ32 CCR5,190GCCR2 and 744ACX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.

Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas.

Abstract: The aim of this study was to evaluate associations between seven morphometric parameters of the nucleoli and nuclei of methyl green and pyronin Y (MG-PY) stained tumour cells of invasive ductal breast carcinoma with relapse-free survival (RFS) and overall survival (OS) time. Histological sections from 150 invasive ductal breast cancers were stained with MG-PY and the following parameters were evaluated by computer image analysis: the nucleolar area, long to short nucleolar axis ratio, nucleolar shape parameter assessing the degree of nucleolar roundness, long to short nuclear axis ratio, number of nucleoli in the nucleus and the percentage of the nuclear cross-section surface area occupied by the nucleoli. A statistically significant association between a nucleolar shape polymorphism and the number of nucleoli in the nuclei of tumour cells and the RFS but not OS was found in the entire group of patients as well as patients with axillary lymph node metastases. A higher polymorphism of nucleolar shape and a higher number of nucleoli in the nuclei of breast cancer cells were associated with decreased relapsefree survival (p < 0.05). The remaining morphometric parameters showed no statistically significant association with RFS or OS. The results indicate that morphometry of nucleoli in MG-PY stained histological sections can be useful in the analysis of associations between nucleolar parameters and prognosis of patients with invasive breast cancer.

CD52 gene polymorphism and its potential effect on the response to alemtuzumab in renal transplant recipients.

Abstract: CD52 is a small glycopeptide leukocyte antigen present on selected subpopulations of human cells. From the clinical point of view this protein is an important target for therapeutic interventions aimed at leukocyte depletion in hematological malignancies and post-transplant immunosuppression. Recently, two variants of CD52--rs1071849 (A119G; Asn40Ser) and rs17645 (A123G; I1e41Met)--were discovered. We now report on the distribution of these variants in kidney graft recipients and controls. Our bioinformatics findings suggest that CD52 polymorphism may affect the efficiency of GPI anchor formation and thus may indirectly alter the response to anti-CD52 agents.

Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor

Abstract: Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal to the splenic flexure. Nuclear TS was detected by immunohistochemistry with a TS 106 monoclonal antibody on tissue microarrays constructed from 269 CRCs. The median histological score of nuclear TS expression of all proximal tumors was two times higher (p = 0.0003) and in men three times higher (p = 0.00023) than that found in distal tumors. In multivariate analysis which included age, sex, Astler-Coller stage, histological grade, and site, only proximal location of the tumor was identified as an independent factor associated with higher TS expression (odds ratio 2.46, 95% confidence interval = 1.29-4.70, p = 0.0062). These results demonstrate significant differences in nuclear TS expression between proximal and distal cancers and suggest the potential importance of the site of the tumor for proper stratification of patients for chemotherapy.

Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation.

Abstract: Introduction The purpose of this study was to investigate whether the polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) was related to the risk of occurrence of potentially dangerous arrhythmias during kidney transplant. Methods We performed this prospective observational study with additional patient monitoring during the kidney transplant procedure and in the postoperative period with continuous electrocardiogram (ECG) - (digital holter; ECG monitor type 300-7 Suprima system; Oxford, UK). After manual trace analysis, we performed classification of arrhythmias by interval measurement (including QT correction according to Bazett's formula: Qtc = QT/RR1/2), ST segment analysis within all channels, and analysis of heart rate variability (HRV) parameters (time analysis: SDNN as total rate variability measure, SDANN as long-term variability measure, SDNNindex, rMSSD and pNN50 as short-term variability measure) as well as frequency measure of power width parameters in the spectrum between 0.0033 Hz and 0.4 Hz. Subsequently applying polymerase chain reaction restriction fragment length polymorphism methods, we investigated A1936G (rs203462) AKAP10 polymorphism among 54 kidney recipients. Results Analysis of variance showed that prolongation of the QTc interval associated with the variant genotypes (GG + AG) was significantly greater compared with the AA genotype among kidney recipients ( P = .04). We did not observe a relationship between the AKAP10 polymorphism and other arrhythmias, or clinical or environmental factors. Conclusions Our data suggested that the AKAP10 (rs203462) GG + AG variation was associated with an increased risk of severe arrhythmias during kidney transplantation.