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Biomedical subjects

J Komorowski

Publications and source records attributed to J Komorowski.

At least 19 recordsLinked to original sources
PubMed2003

GH-RH antagonist (MZ-4-71) inhibits VEGF secretion and proliferation of murine endothelial cells.

Angiogenesis plays a key role in solid tumor formation, invasiveness and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is necessary in the process of neovascularisation. Antagonists of growth hormone-releasing hormone (GH-RH) have been shown to suppress both in vivo and in vitro growth and metastasis of many human cancer cell lines. The mechanisms that mediate the antitumorigenic actions of these antagonists involve direct and indirect pathways, but are not completely elucidated. We have examined the effect of GH-RH antagonist MZ-4-71 on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. MZ-4-71 at 10(-8) to 10(-6) M concentrations inhibited the proliferative activity of cultured cells and suppressed the release of VEGF into supernatants of 72 h endothelial cell cultures. To our knowledge this is the first study reporting antiangiogenic properties of GH-RH antagonists.

Animals↗
PubMed2002

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy.

Angiogenesis is one of the key stages in the development of neoplastic tumours, in which a small group of mutated cells transforms into a large malignant tumour metastasising to the neighbouring tissues and organs. The studies on the significance of neoangiogenesis in the progression of endocrine gland neoplasms have recently become one of the most rapidly evolving branches of molecular endocrinology. The induction of angiogenesis has been demonstrated to result from the imbalance between positive and negative factors which control this process. Our paper presents the results of current studies on the role of factors such as molecular markers of angiogenesis (e.g. vascular endothelial growth factor and basic fibroblast growth factor), metalloproteinases (which regulate the decomposition of the extracellular matrix) and their inhibitors, and adhesive molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble intracellular adhesion molecule-1) in the pathogenesis and diagnostics of endocrine gland tumours in humans. Also, we discuss new therapeutic strategies for inhibiting the growth of neoplasms by blocking the formation of blood vessels using angiogenesis antagonists, which inhibit various stages of angiogenesis. More and more data are being accumulated suggesting that these preparations could, in the near future, be used in the pharmacotherapy of some endocrine gland neoplasms.

Clinical Trials as Topic↗
PubMed2001

[New knowledge derived from measurement of gene expression with the DNA microarray method].

BACKGROUND: The cDNA microarray method offers the first possibility of obtaining a global understanding of biological processes in living organisms, by simultaneous read-outs of tens of thousands of mRNAs. Initial experiments suggest that genes with similar function have similar expression patterns. MATERIAL AND METHODS: Understanding this level of biological complexity will, however, require completely new approaches to data analysis. Computer science methods, such as data mining and knowledge discovery, can synthesize interpretable if-then rules that model the relation between gene expressions and functions and use the rules to classify unknown genes. The huge body of existing biological and medical knowledge makes it necessary to develop methods for extracting knowledge from such repositories. RESULTS: Models of relations between gene expressions and gene functions in a data set from a publicly available source are synthesized semiautomatically and applied to classify unknown genes. Encouraging results have been achieved. The method is applied in the analysis of data from our microarray system which has recently become operational. INTERPRETATION: The principles are of general importance and will be used to evaluate a wide range of complex data sets like decision support in clinical medicine, for situations in which physicians need to handle a large volume of data for each patient.

Computational Biology↗
PubMed2001

A literature network of human genes for high-throughput analysis of gene expression.

We have carried out automated extraction of explicit and implicit biomedical knowledge from publicly available gene and text databases to create a gene-to-gene co-citation network for 13,712 named human genes by automated analysis of titles and abstracts in over 10 million MEDLINE records. The associations between genes have been annotated by linking genes to terms from the medical subject heading (MeSH) index and terms from the gene ontology (GO) database. The extracted database and accompanying web tools for gene-expression analysis have collectively been named 'PubGene'. We validated the extracted networks by three large-scale experiments showing that co-occurrence reflects biologically meaningful relationships, thus providing an approach to extract and structure known biology. We validated the applicability of the tools by analyzing two publicly available microarray data sets.

Computer Communication Networks↗
PubMed2001

Predicting gene function from gene expressions and ontologies.

We introduce a methodology for inducing predictive rule models for functional classification of gene expressions from microarray hybridisation experiments. The basic learning method is the rough set framework for rule induction. The methodology is different from the commonly used unsupervised clustering approaches in that it exploits background knowledge of gene function in a supervised manner. Genes are annotated using Ashburner's Gene Ontology and the functional classes used for learning are mined from these annotations. From the original expression data, we extract a set of biologically meaningful features that are used for learning. A rule model is induced from the data described in terms of these features. Its predictive quality is fine-turned via cross-validation on subsets of the known genes prior to classification of unknown genes. The predictive and descriptive quality of such a rule model is demonstrated on the fibroblast serum response data previously analysed by Iyer et. al. Our analysis shows that the rules are capable of representing the complex relationship between gene expressions and function, and that it is possible to put forward high quality hypotheses about the function of unknown genes.

Algorithms↗
PubMed2000

Effect of somatostatin and octreotide on proliferation and vascular endothelial growth factor secretion from murine endothelial cell line (HECa10) culture.

Angiogenesis, development of new blood vessels, is required for normal tissue repair and also for tumor cell proliferation, extracellular matrix invasion, and hematogenous metastases. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that has been shown to play a key role in neovascularization. Inhibition of angiogenesis in vitro and in vivo was documented by administration of native neuropeptide somatostatin and its analog octreotide. We have studied the effect of somatostatin-14 (SRIF) and ocreotide (sandostatin) on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. SRIF in concentrations from 10(-9) to 10(-5) M and ocreotide in concentrations from 10(-9) to 10(-5) M diminished the proliferative activity of cultured cells vs controls. SRIF and ocreotide in concentrations from 10(-14) to 10(-6) M did not change the release of VEGF into supernatants of 24 or 72 h endothelial cell cultures. Although we showed the antiproliferative effect of SRIF and ocreotide on mouse endothelial cells, we were unable to demonstrate the inhibitory effect of tested peptides on VEGF secretion in vitro.

Animals↗
PubMed2000

Pituitary-adrenocortical responses to the chronic administration of granulocyte colony-stimulating factor in rats.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor, but it may play a role in the regulation of the neuroendocrine system activity. Only few data are available about its possible influence on the pituitary gland. We have recently reported an acute stimulatory effect of G-CSF (and of GM-CSF) on adrenocorticotropic hormone (ACTH) secretion in rats in vivo. The purpose of the present study was to evaluate whether chronic administration of G-CSF affects ACTH and corticosterone secretion and growth processes of the rat anterior pituitary gland and adrenal cortex in vivo. We have demonstrated that G-CSF (at a dose of 10.0 microg/kg body weight (BW)) injected s.c. once daily (for 7 days), stimulated both ACTH and corticosterone secretion. Simultaneously, G-CSF treatment did not change the total anterior pituitary cell proliferation as revealed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). On the other hand, proliferative activity of corticotrophs, detected in the sections of the anterior pituitary using double-labeling. was significantly increased after treatment with G-CSF. Moreover, this growth factor induced an increase in the proliferation ratio in the entire adrenal equatorial section. These findings suggest an involvement of G-CSF in the regulation of pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune system and the endocrine glands.

Adrenal Cortex↗
PubMed2000

Effects of Gn-RH, TRH, and CRF administration on plasma leptin levels in lean and obese women.

Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake, increase energy expenditure and influence the function of hypothalamo-pituitary-gonadal, -thyroid, and -adrenal systems. We have examined the association between leptin concentrations (RIA method) and levels of different hormones using standard Gn-RH, TRH and CRF tests (at 0, 30, 60, and 120 min) in regularly menstruating 10 lean and 10 obese premenopausal women in follicular phase. FSH, LH, estradiol (E2) and progesterone (P) concentrations in Gn-RH test; TSH, PRL, fT3, fT4 in TRH test; ACTH, DHEA-S, cortisol in CRF test were measured by RIA, ELISA or IRMA methods. The obese subjects had thicker four skinfolds, higher fat content in the body, and bigger BMI, compared to the lean females. Gn-RH test: We have noted higher basal leptin values in obese women than in lean subjects, which was stable during the Gn-RH test. In the same blood specimen, basal insulin concentrations did not differ between the tested groups of patients. There were no correlations between E(2), P, or gonadotropins and plasma leptin concentrations between both groups of patients. We have revealed the negative correlation between LH mobilization (maximal incremental values over basal levels; Delta%) and baseline leptin concentrations in all observed subjects. TRH test: In both groups of patients the leptin levels decreased at 120 min of TRH administration. We have noted diminished PRL and TSH mobilisation in obese subjects in comparison to the controls. In all females (n = 20) the correlations between TSH or PRL mobilization and BMI, skinfold thickness and the mass of body fat in kg were negative. In obese subjects only we observed the positive correlations between fT(3)concentrations at 60 and 120 min of the test or Delta% of fT(3)and leptin levels. CRF test: In obese females, we noted higher basal ACTH and cortisol concentrations with decreased mobilization (Delta%) of ACTH or cortisol, as compared to the controls. Basal leptin values were also higher in obese women comparing controls and did not significantly change within 2 h after CRF injection. In all the observed subjects (n = 20), we noted positive correlations between baseline values of leptin and ACTH, as well as negative correlation between basal concentrations of leptin and mobilisation of cortisol. The obtained results show that the hypothalamic neuropeptides may influence leptin secretion in humans.

Adipose Tissue↗
PubMed2000

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble interleukin-2 receptor (sIL-2R) concentrations in peripheral blood as markers of pituitary tumours.

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and soluble interleukin-2 receptor (sIL-2R) are important cytokines. They are secreted by normal pituitary glands and those with all types of adenomas and may be involved in pituitary tissue growth. The peripheral blood concentrations of VEGF, bFGF and sIL-2R in nineteen patients (17-70 years) with pituitary tumours and ten healthy subjects (23-34 years) were studied. Hypersecretion of prolactin (five cases), human growth hormone (four cases), and thyroid stimulating hormone (one case) was recorded in some patients, and the remaining subjects were diagnosed as having nonfunctional pituitary tumours. Increased peripheral blood plasma levels of VEGF (310.82 +/- 59.17 pg/ml) compared with controls (40.32 +/- 11.80 pg/ml; p < 0.01), as well as bFGF (87.27 +/- 7.58 pg/ml) versus controls (11.14 +/- 2.43 pg/ml; p < 0.001) were recorded. The levels of sIL-2R did not differ between the pituitary tumour patients (4,490.58 +/- 581.50 pg/ml) and control subjects (3,617.01 +/- 1,397.18 pg/ml; p > 0.05). The concentrations of VEGF and bFGF in the peripheral blood are useful additional markers of the presence of tumours.

Adolescent↗
PubMed1999

Modelling prognostic power of cardiac tests using rough sets.

Rough sets (Pawlak Z. Rough Sets: Theoretical Aspects of Reasoning about Data, Dordrecht: Kluwer Academic Publishers, 1991) is a relatively new approach to representing and reasoning with incomplete and uncertain knowledge. This article introduces the basic concepts of rough sets and Boolean reasoning (Brown FM. Boolean Reasoning: The Logic of Boolean Equations, Dordrecht: Kluwer Academic Publishers, 1990). A rough set framework is then set up to investigate the prognosis of cardiac events in a set of patients with chest pain that was earlier studied by Geleijnse et al. (J Am Coll Cardiol 1996;28(2):447-454). That study used logistic regression to find that the single most important independent predictor for future hard cardiac events (cardiac death or non-fatal myocardial infarction) was an abnormal scintigraphic scan pattern. However, performing a scintigraphic scan is a relatively expensive procedure, and may for some patients not really be fully necessary as knowledge of the outcome of the scan may be redundant with respect to making a prognosis. Using an approach based on rough sets, this paper explores how a patient group in need of a scintigraphic scan can be identified for subsequent modelling. Identification of such patients may potentially contribute to lowering the cost of medical care and to improving its quality since, virtually without loss of information, fewer patients may be referred for this procedure.

Adolescent↗
PubMed1999

Influence of granulocyte-macrophage colony stimulating factor on pituitary-adrenal axis (PAA) in rats in vivo.

We have studied the in vivo influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on blood plasma concentration of adrenocorticotropic hormone (ACTH) and corticosterone in Wistar rats. The administration of 10 micrograms/kg b.w. GM-CSF at 45 (P < 0.01), 90 (P < 0.01) and at 45 (P < 0.001), 90 (P < 0.001) and 180 min (P < 0.001) increased the secretion of ACTH and corticosterone, respectively. Prolonged administration of 10 micrograms/kg b.w. of GM-CSF increased the ACTH (P < 0.001) and corticosterone (P < 0.001) concentration in blood plasma. We have also found that chronic treatment with 10 micrograms/kg b.w. of GM-CSF increased the proliferative activity of corticotrophs (P < 0.05), but it did not significantly change the total cell proliferation in the anterior pituitary gland. Moreover, this cytokine increased cell proliferation of the adrenal cortex (P < 0.001). These experiments suggest that GM-CSF activates the pituitary-adrenal axis and support the hypothesis of bidirectional associations between the immune and neuroendocrine systems.

Adrenal Cortex↗
PubMed1998

Cytokines serum levels as the markers of thyroid activation in Graves' disease.

In order to examine which cytokine could be used as a marker of the biological effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD) patients, we simultaneously evaluated the concentrations of TSH, free thyroid hormones (fT3 and fT4), anti-thyroid antibodies (anti-TPO and anti-TG) and a group of cytokines: interleukin-2 (IL-2), tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFalphaR, sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal controls. We found that serum sIL-2R concentrations of GD patients had only the tendency to be higher versus controls, but strong positive correlations between fT3 and fT4 and sIL-2R in peripheral blood of GD subjects were revealed. We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients.

Adult↗
PubMed1998

Percutaneous ethanol injection in treatment of benign nonfunctional and hyperfunctional thyroid nodules.

In recent years a new method of treatment of thyroid disorders, percutaneous ethanol injection (PEI), has been successfully used as an alternative to surgery for the management of benign nodules. In this study 103 females and 5 males (34.4 +/- 11.3 yrs) with nonfunctional cystic (23) or solid (38) nodules, and also 47 with hyperfunctional solid nodules, were treated with single or repeated ethanol injections. In all patients, the cytological studies, ultrasound evaluation and the levels of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin or thyroids-stimulating hormone (TSH) before and after ethanol administration, were determined. The patients were followed up for 12-36 months. The size of the benign nonfunctional nodules was totally reduced in 49.9% of cases with solid and in 60.9% of patients with cystic nodules. Hyperthyroidism was cured in 91.5% of patients. The PEI procedure was connected with a few significant complications only, in relation to the localization of nodules. It was cheap, possible on an outpatient basis, easy to perform and acceptable to patients. Since the cost of thyroidectomy is high and the complication rate significant, PEI is a suitable substitute treatment especially for some patients with small toxic benign nodules of the thyroid gland.

Administration, Cutaneous↗
PubMed1998

Effects of thyrotropin, follicle stimulating hormone and luteinizing hormone on sIL-2R in vitro secretion from human peripheral blood mononuclear cells.

The effect of thyroid stimulating hormone (TSH) or thyrotropin (0.06, 0.6, 6, and 60 microIU/ml), follicle stimulating hormone (FSH) and luteinizing hormone (0.1, 1, 10, and 100 mIU/ml) on soluble interleukin-2 receptor (sIL-2R) release in vitro from resting or phytohaemagglutinin (PHA) activated human peripheral blood mononuclear cells (PBMC) was evaluated. sIL-2R concentrations were measured in supernatants of cultured cells by quantitative sandwich enzyme immunoassay method (ELISA). TSH in a dilution of 0.6 microIU/ml and FSH in a concentration of 1 mIU/ml inhibited the secretion of sIL-2R only (p < 0.01) into supernatants from PHA activated PBMC cultures.

Adult↗
PubMed1997

Effects of hCG and beta-hCG on IL-2 and sIL-2R secretion from human peripheral blood mononuclear cells: a dose-response study in vitro.

The effects of human chorionic gonadotropin (hCG) as well as beta-subunit of hCG (B-hCG) in concentrations of: 80,000/25,000; 500; 50; 5 mIU/ml on in vitro release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) from resting or phytohemagglutinin (PHA) activated human peripheral blood mononuclear cells (PBMC) were studied. Both the interleukins were measured in supernatants of human PBMC by quantitative sandwich enzyme immunoassay method (ELISA). We found that hCG in the dilutions of 80,000 mIU/ml (P < 0.01) and 5 mIU/ml (P < 0.05) diminished IL-2 secretion only from PHA activated PBMC. beta-hCG in concentrations of 5 mIU/ml (P < 0.05), 500 mIU/ml (P < 0.01) and 25,000 mIU/ml (P < 0.05) also diminished IL-2 secretion from PHA activated PBMC, and only in a dilution of 25,000 mIU/ml (P < 0.05) from resting PBMC. Simultaneously, hCG in concentration of 80,000 mIU/ml (P < 0.01) potentiated the release of sIL-2R into supernatants from resting and PHA activated PBMC, but in concentration of 50 mIU/ml (P < 0.05) slightly depressed the secretion of IL-2 from PHA activated PBMC cultures. beta-hCG in dilution of 25,000 mIU/ml (P < 0.001) stimulated the release of sIL-2R from resting or PHA activated PBMC. beta-hCG had also inhibitory effect on sIL-2R secretion from resting (in a dilution of 50 mIU/ml; P < 0.05) and PHA activated (500 mIU/ml; P < 0.01) PBMC. The inhibitory effect of very high concentrations of hCG and beta-hCG on IL-2 secretion together with their stimulatory effect on sIL-2R release from PBMC may be an important event during the human pregnancy and various cancers.

Adult↗
PubMed1997

Effect of luteinizing hormone alpha-subunit on IL-2 and sIL-2R in vitro secretions from human peripheral blood mononuclear cells.

The effect of luteinizing hormone alpha-subunit (LH alpha-SU) in concentrations of 50.0, 5.0, 0.5, and 0.05 mIU/ml on the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) secretions in vitro from resting or phytohaemagglutinin (PHA) activated human peripheral blood mononuclear cells (PBMC) was studied. Both interleukins were measured in supernatants of cultured cells by quantitative sandwich enzyme immunoassay method (ELISA). LH alpha-SU in the concentrations tested did not influence the secretion of IL-2 (p > 0.05) or even depress the release of sIL-2R (50.0, 5.0, 0.5 mIU/ml; p < 0.001) into supernatants of PBMC cultures.

Adult↗