Biomedical subjects

J Bartek

Publications and source records attributed to J Bartek.

At least 109 records · Page 6Linked to original sources

PubMed1997

p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression.

Cyclin E is necessary and rate limiting for the passage of mammalian cells through the G1 phase of the cell cycle. Control of cell cycle progression by cyclin E involves cdk2 kinase, which requires cyclin E for catalytic activity. Expression of cyclin E/cdk2 leads to an activation of cyclin A gene expression, as monitored by reporter gene constructs derived from the human cyclin A promoter. Promoter activation by cyclin E/cdk2 requires an E2F binding site in the cyclin A promoter. We show here that cyclin E/cdk2 kinase can directly bind to E2F/p107 complexes formed on the cyclin A promoter-derived E2F binding site, and this association is controlled by p27KIP1, most likely through direct protein-protein interaction. These observation suggest that cyclin E/cdk2 associates with E2F/p107 complexes in late G1 phase, once p27KIP1 has decreased below a critical threshold level. Since a kinase-negative mutant of cdk2 prevents promoter activation, it appears that transcriptional activation of the cyclin A gene requires an active cdk2 kinase tethered to its promoter region.

3T3 Cells↗

PubMed1997

Induction of S-phase entry by E2F transcription factors depends on their nuclear localization.

The E2F transcription factors are essential for regulating the correct timing of activation of several genes whose products are implicated in cell proliferation and DNA replication. The E2Fs are targets for negative regulation by the retinoblastoma protein family, which includes pRB, p107, and p130, and they are in a pathway that is frequently found altered in human cancers. There are five members of the E2F family, and they can be divided into two functional subgroups. Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent fibroblasts and override G1 arrests mediated by the p16INK4A tumor suppressor protein or neutralizing antibodies to cyclin D1, E2F-4 and -5 do not. Using E2F-1 and E2F-4 as representatives of the two subgroups, we showed here, by constructing a set of chimeric proteins, that the amino terminus of E2F-1 is sufficient to confer S-phase-inducing potential as well as the ability to efficiently transactivate an E2F-responsive promoter to E2F-4. We found that the E2F-1 amino terminus directs chimeric proteins to the nucleus. Surprisingly, a short nuclear localization signal derived from simian virus 40 large T antigen could perfectly substitute for the presence of the E2F-1 amino terminus in these assays. Thus, nuclearly localized E2F-4, when overexpressed, displayed biological activities similar to those of E2F-1. Furthermore, we showed that nuclear localization of endogenous E2F-4 is cell cycle regulated, with E2F-4 being nuclear in the G0 and early G1 phases and mainly cytoplasmic after the pRB family members have become phosphorylated. We propose a novel mechanism for the regulation of E2F-dependent transcription in which E2F-4 regulates transcription only from G0 until mid- to late G1 phase whereas E2F-1 is active in late G1 and S phases, until it is inactivated by cyclin A-dependent kinase in late S phase.

Animals↗

PubMed1997

[Significance of monitoring cytokine levels in the prognosis of acute pancreatitis].

The importance of cytokines as mediators and immunomodulators is increasing in all disciplines. Acute pancreatitis is a disease where the trigger mechanisms of the inflammation and thus also the influence of cytokines are very closely associated and are therefore apparent. The authors investigated on that model the levels of IL-2, IL-6, IL-8, IL-2r and neopterin in relation to the stage of the disease and time. They provided evidence in a group of 33 patients that the cytokine level indicates very accurately the stage of the disease and thus also its prognosis. For the assessment proper of the diagnosis the cytokine level is less important as the rise of the level is quite unspecific.

Acute Disease↗

PubMed1997

[Leptin in persons with simple obesity].

Obesity is a disease with distinct genetic determination and its phenotype is defined by the still unknown number of genes whose expression can be influenced by environmental factors. Several years ago, "obesity gene" was isolated in animals. This gene, coding protein which consists of 165 amino acids, is called leptin. Leptin is supposed to be a key substance controlling homeostasis of body weight and energy balance; it is produced by adipocytes and its value correlates highly significantly with anthropometric parameters that characterize physical constitution and amount of subcutaneous fatty tissue. The obese individuals often display hyperleptinemia which is frequently caused by a postreceptor disorder; sporadically, a different leptin structure or hypoleptinemia (caused by genetic anomaly) are reported. It is supposed that either absolute or relative leptin deficiency in obese persons are associated with causal obesity (e.g. appetite stimulation). Leptinemia values correlate with percentage of subcutaneous fatty tissue, insulinemia and sometimes with glycemia. In our study we examined 200 probands, patients of the Metabolic and Diabetologic Out-Patient Department, Hospital in Sternberk. A very close correlation between the amount of subcutaneous fatty tissue (measured by a caliper in 10 skinfolds) and the leptine serum concentration was found. The values of leptinemia in men of normal constitution ranged within 1-11 ng/ml, non-obese women had 3-4 times higher values. Leptinemia in some obese individuals reached up to 70 ng/ml. However, the currently calculated and reported parameters of physical constitution (BMI, WHR, Grant index) did not correlate significantly with leptinemia. Similarly, biochemical parameters considered as general markers of insulin resistance (often associated with obesity) did not correlate significantly with leptinemia. This finding indicates that some calculated parameters, quantifying and gualifying physical constitution, may be ambiguous and leptinemia was found to give more detailed information about the amount of subcutaneous fatty tissue than WHR or BMI. An accidental finding was an important positive correlation between myoglobin concentration and creatinemia. At monitoring the effect of hypolipidemic agents we use the myoglobin examination and therefore we consider this correlation to be very important and every physician performing this analysis should be informed about it. The present study thus confirmed that a more accurate quantification of subcutaneous fatty tissue is required. On the other hand, we believe that examination of leptinemia can contribute significantly to stratification of patients into risk groups (with respect to clinical, economic and time differentiation) and subsequently to the treatment of these patients. In future, criteria for quantification of leptinemia and leptine resistance should be defined precisely.

Adipose Tissue↗

PubMed1996

The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis.

The p16Ink4/CDKN2, D-type cyclins, their partners Cdk4/Cdk6, and pRb constitute a G1 regulatory pathway commonly targeted in tumorigenesis. Genetic, immunochemical, and functional cell cycle analyses showed abnormalities of this pathway in each of 22 human melanoma cell lines examined. Normal melanocytes and all melanoma lines expressed Cdk4, Cdk6, and cyclins D1 and D3. The tumor suppressors p16Ink4/CDKN2 and pRb were lost in 17 and 4 cases, respectively, due to various genetic mechanisms, including transcriptional block of p16 and nonsense mutations of RB1. Ectopic expression of p16 prevented S-phase entry of Rb+/p16- but not Rb-deficient melanoma lines. The SK29-MEL-1 cell line harboring an R24C mutation in Cdk4 expressed wild-type pRb and overabundant p16, the latter preventing endogenous Cdk6 but not Cdk4 from associating with cyclin D1. Microinjection of cyclin D1-neutralizing antibody arrested the SK29-MEL-1 cells in G1, whereas pl6 did not, indicating that the cyclin D1/Cdk4-R24C complex is required for G1 progression, and the resistance of the complex to p16 in vivo. These data strongly support the candidacy of Cdk4 as a novel proto-oncogene, provide further evidence for the p16-cyclin D/Cdk-pRb pathway as a functional unit, and suggest that deregulation of this checkpoint may represent a common step in the multistep progression of sporadic malignant melanomas.

Base Sequence↗

PubMed1996

High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50. p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83%) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67%) harbored homozygous deletions, 5 (21%) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.

Blotting, Southern↗

PubMed1996

Abrogation of p27Kip1 by cDNA antisense suppresses quiescence (G0 state) in fibroblasts.

Progression of eukaryotic cells through the cell cycle is governed by the sequential formation, activation, and subsequent inactivation of a series of cyclin-dependent kinase (Cdk) complexes. p27(Kip1) (p27) is a Cdk inhibitor that blocks, in vitro, the activity of cyclin D-Cdk4, cyclin D-Cdk6, cyclin E-Cdk2 as well as cyclin A-Cdk2, a complex active during S phase. The level of p27 protein expression, usually high in G0/G1 resting cells, declines as cells progress toward S phase and enforced expression of p27 in fibroblasts causes G1 arrest. This situation prevails in CCL39, a Chinese hamster lung fibroblast cell line (this report). However, in addition to p27, several other Cdk inhibitors known to alter G1 progression coexist in most mammalian cells. To investigate the specific contribution of p27 in the control of the mitogen-sensitive G0/G1 arrest, we specifically reduced its synthesis by expressing a full-length p27 antisense cDNA in CCL39 cells. Interestingly, reduction of up to 90% of p27 protein expression increased both basal and serum-stimulated gene transcription of cyclin D1, cyclin A, dihydrofolate reductase, and DNA synthesis reinitiation. Moreover, overexpression of this antisense allows cells to grow for several generations in a serum-free medium supplemented with insulin and transferrin only, thus suggesting that p27-depleted cells cannot exit the cell cycle. These effects were fully reversed by coexpression of a plasmid encoding p27 sense. We conclude that p27, by setting the level of growth factor requirement, plays a pivotal role in controlling cell cycle exit, a fundamental step in growth control.

Animals↗

PubMed1996

Enhanced protein stability: a novel mechanism of D-type cyclin over-abundance identified in human sarcoma cells.

The mammalian D-type cyclins promote progression through a G1 checkpoint by phosphorylating the retinoblastoma protein (pRB), and can contribute to oncogenesis via their deregulated expression achieved through gene amplification, chromosomal rearrangement, or retroviral integration. We now report a novel mechanism of tumour-associated D-cyclin over-abundance, resulting from enhanced protein stability. In two human cell lines established from a single uterine sarcoma biopsy, pRB-positive SK-UT-1B and pRB-deficient SK-UT-1, aberrant accumulation of functional cyclins D1, and D2 and D3 occurred in the absence of gene amplification and/or elevated mRNA expression. The abundance of D-cyclin proteins remained elevated throughout the cell cycle, and pulse-chase experiments revealed six to 10-fold prolongation of their protein half-lives as compared with either diploid fibroblasts or control U-2-OS sarcoma cells. These results point to a critical regulatory role of D-type cyclin turnover, and contribute to refinement of current views of the role played by the cyclin D-CDK-p16-pRB pathway in cell cycle control and tumorigenesis.

Cyclin D↗

PubMed1996

Expression of CDK7/CAK in normal and tumor cells of diverse histogenesis, cell-cycle position and differentiation.

The cyclin-dependent kinase 7 (CDK7) represents the 40-kDa catalytic subunit of the CDK-activating kinase, the enzyme responsible for activatory phosphorylation of multiple CDKs controlling G1, S and G2/M phases of the cell cycle. Here, we surveyed a wide range of normal and tumour cell types, in both cell culture and biopsy specimens, for abundance and subcellular localisation of the CDK7 protein. Immunoblotting and immunocytochemical analyses showed that CDK7 was (i) ubiquitously expressed in all cell types examined; (ii) exclusively nuclear; (iii) moderately elevated in tumour cells when compared with their normal cell counterparts; (iv) invariant throughout the cell cycle of normal lymphocytes, fibroblasts, breast epithelium and several cancer cell lines; and (v) clearly detectable even in quiescent cells, including highly differentiated cell types in situ. Our data are consistent with the emerging role for CDK7/CAK in multiple biological processes, possibly providing a link between cell-cycle control, transcriptional regulation and genomic integrity control.

Breast↗

PubMed1996

The retinoblastoma protein modulates expression of genes coding for diverse classes of proteins including components of the extracellular matrix.

The product of the retinoblastoma susceptibility gene, pRb, is a negative regulator of cell growth. It functions by regulating the activity of transcription factors. Rb represses some genes by sequestering or inactivating the positive transcription factor E2F and seems to activate some others by interacting with factors like Sp1 or ATF-2. However, there are only a few examples of genes which are positively regulated by pRb. In order to find out if there are common mechanisms for promoter regulation by pRb, we were interested to identify more genes which are either stimulated or repressed by pRb. Using the method of differential display (DDRT-PCR) in combination with nuclear run-on analyses we were able to detect a number of genes which are upregulated by ectopic expression of the Rb gene in Rb-deficient mammary carcinoma cells. We could demonstrate not only stimulation of the endogenous mutant Rb gene but also positive regulation of genes coding for diverse classes of proteins, including the endothelial growth regulator endothelin-1 and the proteoglycans versican and PG40. As a second approach, we investigated gene expression in cell lines established from Rb deficient heterozygous and homozygous knockout mouse embryos and normal mice. We have identified several genes the expression of which correlates positively or negatively with the presence of Rb. These data provide further evidence for pRb being a master regulator of a complex network of gene activities defining the difference between dividing and resting or differentiated cells.

Animals↗

PubMed1996

Abundance and subcellular localisation of cyclin D3 in human tumours.

The D-type cyclins are positive regulators of the G1 phase of the mammalian cell cycle. Cyclins D1 or D2 are over-expressed in several types of cancer, transform rodent cells in culture and therefore harbor hallmarks of cellular proto-oncogenes. In contrast, no data on expression of cyclin D3 in tissues and tumours are presently available. We have raised monoclonal antibodies (MAbs) specific for cyclin D3 and examined abundance and subcellular localisation of this G1 cyclin in a series of human cultured cell types and in 180 primary tumours of diverse histogenesis. Cyclin D3 localised predominantly in nuclei of normal and tumour cells both in culture and in situ, and a pronounced cell-to-cell variation of its abundance was reminiscent of cyclins D1 and D2. Immunohistochemical analysis of tumour and corresponding normal tissues showed strong aberrant accumulation of cyclin D3 in a subset (about 10%) of breast carcinomas, whereas only weak-to-moderate expression was found in colorectal, head and neck and uterine carcinomas, melanomas and soft tissue sarcomas. The specificity of the immunohistochemical data was confirmed by immunoblotting analysis of tissue and tumour lysates. Our results indicate that over-abundance of cyclin D3 is considerably less frequent than that of cyclin D1, yet we identify subsets of breast tumours, and potentially lymphomas, as candidate tumour types with elevated cyclin D3 expression.

Biomarkers, Tumor↗

PubMed1996

bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma.

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1-S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas (n = 40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.

Base Sequence↗

PubMed1996

The retinoblastoma protein pathway and the restriction point.

The emerging role of the retinoblastoma protein (pRb) as a major controller of the restriction point has been supported by recent discoveries, including pRb's ability to repress gene transcription by all three RNA polymerases, which suggests a link between DNA replication and cell growth. Convergent genetic and biochemical data provide new insights into the molecular events that are upstream of, at, and downstream of pRb phosphorylation, which is regulated by G1-phase cyclins and cyclin-dependent kinases (Cdks) and their inhibitors (CKIs). Major advances have also been made in our understanding of a key role of the pathway involving cyclin D, Cdks, CKIs, pRb and E2F both in commitment to traversing the cell cycle and in restraining oncogenesis.

Cell Cycle↗

PubMed1996

Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint.

The commitment of mammalian cells in late G1 to replicate the genome and divide in response to mitogenic growth factors operating via tyrosine kinase receptors depends on phosphorylation of the retinoblastoma protein (pRb), a process controlled by cyclin D-associated cyclin-dependent kinases (cdks) and their inhibitors. This study addressed the issue of whether also other mitogenic signalling cascades require activation of cyclin D-associated kinases or whether any mitogenic pathway can bypass the cyclin D-pRb checkpoint. We show that mitogenic signal transduction pathways from three classes of receptors, the membrane tyrosine kinase receptors activated by serum mitogens or epidermal growth factor, estrogen receptors triggered by estradiol, and the cyclic AMP-dependent signalling from G-protein-coupled thyrotropin receptors, all converge and strictly require the cyclin D-cdk activity to induce S phase in human MCF-7 cells and/or primary dog thyrocytes. Combined microinjection and biochemical approaches showed that whereas these three mitogenic cascades are sensitive to the p16 inhibitor of cdk4/6 and/or cyclin D1-neutralizing antibody and able to induce pRb kinase activity, their upstream biochemical routes are distinct as demonstrated by their differential sensitivity to lovastatin and requirements for mitogen-activated protein kinases whose sustained activation is seen only in the growth factor-dependent pathway. Taken together, these results support the candidacy of the cyclin D-cdk-pRb interplay for the convergence step of multiple signalling cascades and a mechanism contributing to the restriction point switch.

Animals↗

PubMed1996

Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression.

The E2F family of transcription factors regulate genes, whose products are essential for progression through the mammalian cell cycle. The transcriptional activity of the E2Fs is inhibited through the specific binding of the retinoblastoma protein, pRB, and the pRB homologs p107 and p130 to their transactivation domains. Seven members of the E2F transcription factor family have been isolated so far, and we were interested in investigating the possible contribution of the various E2Fs to cell cycle control. By presenting the results of the generation of cell lines with tetracycline-controlled expression of E2F-1 and E2F-4 and microinjection of expression plasmids for all members of the E2F family, we demonstrate here that the pRB-associated ED2Fs (E2F-1, E2F-2, and E2F-3) all induce S phase in quiescent rate fibroblasts when expressed alone. In contrast, the p107/p130-associated E2Fs require the coexpression of the heterodimeric partner DP-1 to promote S-phase entry and accelerate G1 progression. Furthermore, the pRB-associated E2Fs were all able to overcome a G1 arrest mediated by the p16INK4 tumor suppressor protein, and E2F-1 was shown to override a G1 block mediated by a neutralizing antibody to cyclin D1. The p16INK4-induced G1 arrest was not affected by expression of E2F-4, E2F-5, or DP-1 alone, but simulataneous expression of E2F-4 and DP-1 could overcome this block. Our results demonstrate that the generation of E2F activity is rate limiting for G1 progession, is sufficient to induce S-phase entry, and overcomes a p16-mediated G1 block, and since E12F-1, E2F-2, and E2F-3 are associated with pRB, they are the most likely downstream effectors in the p126-cyclin D-pRB pathway. Furthermore, our date suggest that the two subsets of E2Fs are regulated by distinct mechanisms and/or that they have distinct functions in cell cycle control. Since E2F-4 and E2F-5 cannot promote S-phase entry by themselves, our results may provide an explanation for the apparent lack of aberrations in p107 or p130 in human cancer.

Animals↗

PubMed1996

Phenotype-related differences in the expression of D-type cyclins in human B cell-derived lines.

Exposure of normal resting B lymphocytes to EBV in vitro leads to activation, subsequent immortalization, and the establishment of lymphoblastoid cell lines (LCLs). The endemic form of Burkitt's lymphoma (BL) is associated with EBV. EBV-positive BL lines maintain the original tumor phenotype (group I BL) initially and express only one EBV-encoded protein, EBV nuclear antigen (EBNA)-1. Most of them drift toward a LCL-like phenotype during in vitro culturing and express all nine EBV-encoded growth transformation-associated proteins (group III BL). Cyclin D2 and D3 have been found previously to differ in their mRNA expression in BL and LCL. Cyclin D2 expression has been attributed to EBV gene expression and to EBNA-2 and EBNA-5 in particular. We have studied cyclin D2/D3 expression in larger series of LCLs, BL lines, and freshly EBV-infected peripheral blood B lymphocytes, both at the mRNA and protein levels. The predominant cyclin D2 expression in the LCLs and group III BLs correlated with an activated B-cell phenotype. In contrast, only cyclin D3 was expressed in the group I BL lines. EBV-carrying group II BL lines that retained the BL-associated CD10 did not express cyclin D2. A collection of in vitro EBV-converted sublines of originally EBV-negative BLs that expressed a full set of the growth transformation-associated EBV proteins maintained their CD10 and cyclin D3 expression. Blood B lymphocytes expressed no D2 or D3 as judged by immunostaining. Cyclin D2 could be detected by immunostaining in a proportion of the activated blasts 40 h postinfection. Cyclin D3 that is expressed at a low level in the established LCLs was stained easily in B blasts at this time. The level of cyclin D3 at 72 h postinfection was two to three times higher than in the exponentially growing LCLs, as detected by immunoblotting. It was still 5-10 times lower than in group I BLs. Mitogen stimulation of primary B cells induced cyclin D3 at a similar level as in the LCLs. Our data are consistent with the notion of cell lineage-specific D-type cyclin expression. They also indicate that B cells may switch their D-type cyclin expression during differentiation.

B-Lymphocytes↗

PubMed1996

[Nutritional status in patients with stroke. Diagnosis, therapy and its monitoring].

Stroke (Ischemic) initiates numerous pathophysiological processes and each of them can be dangerous. When evaluating patient's state and choosing therapeutical strategy, a complexity of the followed-up parameters should be taken into account as well as a complexity of a given therapeutical approach. On the basis of literary data and acquired clinical experience, we developed our own algorithm for diagnosis of the nutritional state and it was implemented into a semi-expert computing system SOFT. Using SOFT program, the group of 23 patients with ischemic CMP was examined within 40 hrs after its origin. These patients were found to show a slight protein catabolism and nutritional stress (aminograms, stress index, nutritional percentage of complications, nitrogen balance, CRP, prealbumin). necessity of an early diagnosis of nutritional deficiency and disorders of protein metabolism in STROKE patients is discussed. The paper reports on means of enteral nutrition prepared in the Hospital in Sternberk which appeared to be highly favorable. The aspects of administration of parenteral nutrition are discussed.

Brain Ischemia↗

PubMed1996

The level of neopterin in blood serum as one of the possible prognostic markers of Crohn's disease activity.

Neopterine is considered to be one of the markers of immunity system activity. An increased level of this pteridine derivate is determined in blood or urine in infections, transplant rejections, and in other conditions accompanied by changes in the immunity system. Monitoring its level in various body liquids can be important when assessing the immunity system condition, nevertheless, its non-specificity causes difficulties when interpreting the results. Up to now, very few papers have been published dealing with the determination of neopterine levels in patients with IBD. We studied a group of 25 patients who are monitored in a longterm manner at our clinic suffering from Crohn's disease. During 1993 and 1994, we were determining their levels of neopterine in blood together with other parameters. It was a group of patients chosen at random in different stages of disease, and we were interested in the correlation of the height of neopterine level with the activity of Crohn's disease. We proved statistically unimportant correlation between the height of neopterine level in blood serum and Crohn's disease activity. The question is discussed whether the examination of this marker be useful when monitoring Crohn's disease activities.

Biomarkers↗