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Biomedical subjects

K Bogunia-Kubik

Publications and source records attributed to K Bogunia-Kubik.

17 recordsLinked to original sources

Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a lymphoproliferative disorder characterized by clonal expansion of B lymphocytes. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter/enhancer region of tumour necrosis factor-alpha (TNFA) gene and susceptibility to B-CLL. TNFA (-308 G/A) promoter single nucleotide polymorphism (SNP) was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) using commercial oligonucleotides. No significant association was found between the distribution of TNFA alleles and B-CLL in Polish patients with B-CLL. Our single centre results were compared with other literature data and combined in a cumulative analysis employing the Mantel-Haenszel method. Among 183 B-CLL patients, 47 (26%) were carrying TNFA*2 allele and this allele was present in 98 out of 348 controls (28%). Also, the results of the Mantel-Haenszel test did not show a significant correlation [Mantel-Haenszel estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results suggest that TNFA (-308) alleles are not involved in the predisposition to the development of B-CLL.

Adult↗

HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis.

In the present study, two coding polymorphisms within the heat shock protein 70-hom gene (HSP70-hom) were analysed. One hundred and thirty-eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70-hom gene were typed using amplification refractory mutation system and polymerase chain reaction-restriction fragment length polymorphism technique, respectively. A significant prevalence of the HSP(+2437)-C allele and the HSP(+2437)-CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA-DRB1*03-positive patients with LS were carrying both HSP(+2437)-C and (+2763)-G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)-C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)-G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)-G allele was present with either DRB1*03 or HSP(+2437)-C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)-C and (+2763)-G in patients with LS. In conclusion, HSP(+2437)-C allele was found as a factor associating with susceptibility to sarcoidosis and LS.

Acute Disease↗

Nanotechnology on duty in medical applications.

At the beginning of 21(st) century, fifty years after discovery of deoxyribonucleic acid (DNA) double helix structure, scientific world is faced with a great progress in many disciplines of biological research, especially in the field of molecular biology and operating on nucleid acid molecules. Many molecular biology techniques have been implemented successfully in biology, biotechnology, medical science, diagnostics, and many more. The introduction of polymerase chain reaction (PCR) resulted in improving old and designing new laboratory devices for PCR amplification and analysis of amplified DNA fragments. In parallel to these efforts, the nature of DNA molecules and their construction have attracted many researchers. In addition, some studies concerning mimicking living systems, as well as developing and constructing artificial nanodevices, such as biomolecular sensors and artificial cells, have been conducted. This review is focused on the potential of nanotechnology in health care and medicine, including the development of nanoparticles for diagnostic and screening purposes, the manufacture of unique drug delivery systems, antisense and gene therapy applications and the enablement of tissue engineering, including the future of nanorobot construction.

Animals↗

Lack of IFN-gamma 2/2 homozygous genotype independently of recipient age and intensity of conditioning regimen influences the risk of aGVHD manifestation after HLA-matched sibling haematopoietic stem cell transplantation.

A total of 110 patients (71 adults and 39 children) who received allogeneic haematopoietic stem cell transplantation from HLA-matched sibling donors were studied for the incidence of acute graft-versus-host disease (aGvHD) in relation to IFN-gamma gene microsatellite polymorphism. A strong tendency was observed towards the lower incidence of grades II-IV aGvHD in patients having an IFN-gamma 2/2 genotype as compared to the recipients with other IFN-gamma genotypes (0.12 vs 0.33, P=0.06). This relationship was independent of the intensity of conditioning regimen and diagnosis. IFN-gamma polymorphic features, together with other clinical and biological factors (patient's age, donor-recipient gender, diagnosis, conditioning regimen, transplant material and GvHD prophylaxis), were subjected to multivariate analysis for aGvHD manifestation in order to exclude indirect association of the IFN-gamma 2/2 genotype. In multivariate analysis, myeloablative therapy (OR=11.462, P=0.013), recipient age (OR=4.896, P=0.009) and lack of IFN-gamma 2/2 genotype (OR=4.311, P=0.048) were found to significantly contribute to the development of grade II-IV aGvHD, while type of GvHD prophylaxis showed less-strong influence (OR=2.963, P=0.066). Thus, it appeared that the IFN-gamma 2/2 genotype constituted an independent and protective factor associated with a decreased risk of grade II-IV aGvHD. However, this genotype was not found to be associated with the risk of cGvHD or survival.

Acute Disease↗

HLA-DR11 in addition to donor age, gender, and major blood group incompatibility influence the incidence of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

The present study sought to retrospectively assess risk factors for occurence of and mortality from severe acute graft-versus-host-disease (aGvHD) among 66 patients receiving hematopoietic stem cell transplants (HSCT) from matched sibling donors (MSD). Thirty-six patients were in early and 30 in intermediate or advanced stages of the disease. Twenty-six patients developed severe aGvHD grades II-IV. Thirty-five patients died after transplantation (15 due to aGvHD). There were 20 major ABO-mismatched transplants and 26 cases wherein donor and recipient differed with respect to sex (11: F-->M; 15: M-->F). These transplant characteristics as well as HLA class II specificities were chosen for discriminative analysis. HLA specificities were assessed in an independent analyses for as patients lacking (DR11) or having DR13 associated with aGvHD. It appeared that donor age increased the risk of aGvHD, but a fatal outcome of this complication was influenced by recipient age. Female to male transplantations were associated with a higher risk of aGvHD. Major ABO incompatibility tended to increase the risk of aGvHD and fatal outcomes. DR11 was associated with factors playing a protective role, while DR13 was the least of all significant factors influencing the development of severe and fatal aGvHD.

ABO Blood-Group System↗

TNF polymorphisms are associated with toxic but not with aGVHD complications in the recipients of allogeneic sibling haematopoietic stem cell transplantation.

NcoI polymorphism within the promoter/enhancer region of TNFalpha and the first intron of TNFbeta encoding gene was analysed in 70 patients with haematological malignancies transplanted from HLA-identical sibling donors. The control group was composed of 130 healthy individuals. We showed that patients heterozygous for one or both TNF genes suffered more frequently from severe (grades III-IV) toxic complications than those carrying the other TNF genotypes (TNFA(*)1,2: 9/10 vs 30/60, P<0.05; TNFB(*)1,2: 20/26 vs 19/44, P<0.01; TNFA(*)1,2 TNFB(*)1,2: 9/9 vs 30/61, P<0.005). Conversely, patients having TNFB(*)2,2 less frequently presented with severe toxic lesions (17/39 vs 22/31, P<0.05). Additional analyses showed that TNFA(*)1,2, independent of the TNFB genotype composition, influenced the manifestation of grades III-IV toxic lesions, while TNFB(*)2,2 and TNFA(*)1,1 in combined association played a protective role. Logistic regression analysis confirmed the association of recipient TNFA(*)1,2 genotype with severe toxic complications, in addition to aggressive myeloablative conditioning regimen and female to male transplantation. No relation was found between TNF polymorphic features and aGvHD incidence by either uni- or multivariable analyses.

Adolescent↗

HLA-DRB1*03, DRB1*11 or DRB1*12 and their respective DRB3 specificities in clinical variants of sarcoidosis.

Determination of DRB1 and DRB3 specificities in sarcoidosis patients identified that the presence of DRB1*03 and the absence of DRB1*11 and/or DRB1*12 favors a course of disease that is associated positively with Löfgren's syndrome (DRB1*03) and negatively with stage I disease (DRB1*11 and/or 12). In common with normal controls, DRB1*03 was associated with DRB3*0101 and DRB1*11/12 with DRB3*0201/2. An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed that DRB1*03 and DRB3*0101 were associated with Löfgren's syndrome in a combined association fashion. Conversely, a lack of DRB1*11 and/or DRB1*12 but not DRB3*0201/2 favored the clinical course of sarcoidosis.

Adolescent↗

[Cytokine production by adult and cord blood (CB) cells--comparison and explanation of differences].

Cytokine production may be analysed with the use of different techniques including ELISA, bioassay, mRNA analysis or intracellular cytokine staining. Regardless of the used stimulation and analysis method, cytokine production has been found to be reduced in cord blood compared to the adult cells. In general cord blood cells produce less cytokine, have a lower bioactivity or a reduced frequency of cytokine producing cells as compared to adult cells. This paper gives an overview of the cytokine production by different subpopulations of adult and CB cells, and presents some ideas leading to an explanation of the apparent differences in cytokine production by adult or cord blood cells.

Aging↗

Macrophage colony stimulating factor (M-CSF) within cord blood sera may be partially responsible for the reduced proliferation of cord blood T cells.

We show that there are differences in the soluble factors in cord blood (CB) and adult serum and that these differences play a role in T cell function. Thus, the mitogen and alloantigen-specific proliferative response of adult T cells was enhanced with increasing concentrations of adult serum and CB serum, but to a lesser extent with CB serum. In addition, proliferation of T cells induced by stimulation through the T cell receptor alone (via CD3 stimulation), could be enhanced with adult but not CB serum. However, CB serum enhanced the IL-2-specific proliferative response of pure T cells whereas adult serum did not. To determine whether there was an anti-inflammatory cytokine within CB serum which could induce these results, we assayed our serum samples for anti-inflammatory cytokines. IL-13 could not be detected in any serum sample, whereas IL-10 could be detected in adult but not CB serum (P < 0.002). However, there was a significant difference in the levels of macrophage colony stimulating factor (M-CSF) detected in adult and CB serum samples (P < 0.01). M-CSF was detected in 6/7 CB serum samples (mean +/- SD was 3.8 +/- 2.3 ng/ml) and 0/5 adult serum samples. Furthermore, anti-M-CSF antibody restored the reduced allo-response of T cells incubated in CB serum. Thus, M-CSF may act as a suppressor factor in CB serum. Whether this is sufficient to explain the lack of an allo-response by the foetus to the mother, or the reduced graft-versus-host disease when CB is used instead of bone marrow in stem cell transplantation, is yet to be determined.

Adult↗

[Quality control for HLA typing].

In November 1999 we started the quality control exercise for Polish institutions involved in HLA typing. Five out of eleven invited institutions responded favourably and took part in the first run of the workshop. In the second trial, presently reported, number of labs increased to eight. Each centre received 4 blood samples for serological typing of HLA class I and 5 samples for DNA HLA class II typing. As in the previous workshop, HLA class II typing should be performed at least for DRB1 alleles at the low resolution level. The paper presents the results of the second run of standardisation.

HLA-DQ Antigens↗

TNF-alpha and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis.

We have analyzed the HLA-DRB1 alleles and -308 TNF-alpha gene polymorphism in 78 sarcoidosis patients and 50 controls. The sarcoidosis group as a whole did not show any significant correlation with the TNF-A or the HLA-DR alleles compared to the control group. However, the patient subgroups of Löfgren and non-Löfgren sarcoidosis exhibited significant allele associations. In the Löfgren patient group, the TNF-A2 and the HLA-DR3 alleles were represented significantly higher, with a highly significant relative risk resulting from the presence of the TNF-A2 or the HLA-DR3 allele or both. In the non-Löfgren patient group, the phenotype expressing HLA-DR2 and lacking TNF-A2 was significantly higher than in the Löfgren patient group. Due to these significant genetic differences in the subgroups of Löfgren and non-Löfgren sarcoidosis patients, we conclude that the genotyping of these two loci (-308 TNF-alpha promoter polymorphism and HLA-DR) may be of prognostic value for the course of disease in sarcoidosis.

Acute Disease↗

Confirmatory typing results of the National Polish Bone Marrow Donors Registry.

Preliminary analysis of HLA class I typing of 618 individuals (patients and healthy members of 153 families) referred to the National Polish Bone Marrow Donors Registry (NPBMDR) for a donor search revealed that the number of undetected locus A and B antigens was more frequent than it was reported in a large scale population study in Poland (0.28 vs 0.076, p=0.000). This was associated with a lack of typing of family members for 51 out of 153 patients. 171 individuals primary typed (140 by serology and 31 by DNA typing) in 6 different Polish institutions were retyped in our laboratory with the use of PCR-SSO or PCR-SSP techniques. The results were discrepant in 50 cases (29%) including 19 patients and 31 family members. In 46% one DR specificity was missing, false typing of one or two specificities was evident in 46% and 14% of erroneous typing, respectively. The highest rate of errors was found in DRw52 group of specificities with the most difficult DR13 (32% of all false typing and 67% of errors within DRw52 group).

Bone Marrow↗