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Unlabelled: Fatty tissue derived adipocytokines regulate appetite, but in abnormal concentration impair systemic metabolic homeostasis and make the patients prone to inflammatory related disorders. The aim of study was to examine whether weight loss in patients after implementation of a gastric balloon is reflected in changes in chosen anthropometrical parameters and in the concentration of leptin and adiponectin in serum., Materials and Methods: The study group consisted of 18 extreme obese patients (BMI>39.9, mean age 39.5±12.1 years, 12 men, 6 women), undergoing implementation of a gastric balloon for 6 months. The control group consisted of 18 healthy volunteers. The adiponectin and leptin concentrations in the sera and the calculated % body fat and indicators: BMI, WHR, VAI, BAI, WHtR were determined prior to implementation and after the balloon removal and then further parameters were calculated: % excessive weight loss, % weight loss., Results and Conclusions: All the parameters and leptin concentration in the tested group were markedly upregulated and adiponectin concentration was significantly lower compared to controls. Reduction in the body mass in patients subjected to BIB, reflected in leptin and anthropometrical parameters down-regulation, (except WHR and VAI), was accompanied with normalization of adiponectin concentration that affect metabolism and is important regulator of hunger and satiety., (© 2015 MEDPRESS.)

Numerous studies have revealed that MDM2 oncoprotein is upregulated in different types of cancer. Additionally, it was demonstrated that in some cases, MDM2 may inhibit the neoplastic transformation process. In other words, MDM2 protein can be considered as an oncogene or as a tumor suppressor depending on the appropriate cellular context. MDM2 functions on different levels in the cell, which is a consequence of its complex structure, a plethora of interacting partners and regulation through numerous postranslational modifications. Thus, an alteration of the delicate balance in MDM2 activity can influence transformation and cancer development. Genomic instability is a hallmark of cancer, which inversely correlates to the activity of DNA damage response. In the case of not transformed cells MDM2 inhibits double strand brakes (DSBs) repair, hence stimulating carcinogenesis. In cancer cells MDM2 stimulates cytostatic-induced DSBs repair, thus leading to chemoresistance.

Ovarian cancer is a neoplasm with high mortality rate. Its progression is mostly asymptomatic, which results in its first diagnosis in a late stage of the disease. Currently there are no reliable diagnostic methods for early detection of ovarian cancer. Molecular mechanisms leading to its development are not yet fully discovered. Recent studies show that mesothelin gene is up-regulated in patients with serous ovarian cancer. Mesothelin is a glycoprotein found in cell membranes of mesothelial cells lining the peritoneum, pericardium and pleura. Association of mesothelin in the development of ascites, intraperitoneal spread of the neoplasm, and its capability to modulate immune response have been show. It has been found that patients diagnosed with ovarian cancer have elevated serum mesothelin specific IgG levels. Mesothelin is also able to induce a cellular immune response, which is used in researches of ovarian cancer vaccines. High mesothelin expression in cancer tissues and its regular low expression in physiologic ones makes the glycoprotein a worthy candidate for the purpose of ovarian cancer treatment. Current studies assess the use of mesothelin as a target antigen as well as its immunogenicity. The methods of treatment include the use of recombined immunotoxin synthesized from the Pseudomonas exotoxin A (SSIP), MORAb-009 - chimeric monoclonal antibody, immunoconjugates (antibody - drug conjugates), cancer vaccines and gene therapy. The results of these studies are promising but further trials in larger population are required to confirm this.

Malignant cells are known to enhance glucose metabolism, to increase glucose uptake and to inhibit the process of oxidative phosphorylation. Accelerated glycolysis is one of the biochemical characteristics of cancer cells that allow them to compensate the inefficient extraction of energy from glucose in order to continue their uncontrolled growth and proliferation. Upregulation of glucose transport across the plasma membrane is mediated by a family of facilitated glucose transporter proteins named GLUT. Overexpression of GLUTs, especially the hypoxia-responsive GLUT1, has been frequently observed in various human carcinomas. Many studies have reported a correlation between GLUT1 expression level and the grade of tumor aggressiveness, which suggests that GLUT1 expression may be of prognostic significance. Therefore, GLUT1 is a key rate-limiting factor in the transport and glucose metabolism in cancer cells. This paper presents the current state of knowledge on GLUT1 regulation as well as its utility in the diagnosis and therapy of cancers.

The colossal progress in understanding of vitamin D and phosphate metabolism introduces new perspectives in chronic kidney disease (CKD) therapy. Increasing demand for phosphate excretion per nephron triggers the vicious cycle that leads to increase in FGF-23 and PTH and decrease in vitamin D and Klotho. Restriction of dietary phosphate intake (low phosphate diet) and administration of phosphate binder can be regarded as the most important interventions in this case. Because the vicious cycle is likely activated long before hyperphosphatemia occurs during CKD progression, phosphate restriction would have been more effective if started before serum phosphate levels increased, perhaps as soon as serum FGF-23 levels rose. Phosphate restriction alleviates phosphate overload per nephron and can disrupt the vicious cycle: phosphate restriction can reduce serum FGF-23 levels and increase vitamin D, which in turn increase Klotho expression in kidney and parathyroid glands. Inhibitors of rennin-angiotensin system (rosiglitazone, angiotensin-converting enzyme inhibitors) and proper vitamin D supplementation may also up-regulate Klotho expression. Increased Klotho in the kidney may improve FGF-23 sensitivity, which further reduce the amount of FGF-23 required for excreting a given amount of phosphate. Increased Klotho in parathyroid may improve the ability of FGF-23 to suppress PTH. Proper supplementation with vitamin D increase the concentration of substrate for local 1,25(OH)2D synthesis 25(OH)D, which directly suppress PTH, increase Klotho, and decrease FGF-23 by proanabolic action on bone. Improving vitamin D status by inhibition of CYP24A is also under evaluation, as well as antibodies against FGF-23, as modern therapies in CKD.

Carcinogenesis in various tissues is accompanied by alterations in protein and lipid glycosylation, such as changes in the expressions of Lewis histo-blood group antigens. Neoplastic transformation is often followed by changes in expression of one or more of these oligosaccharides in a pattern that is typical for the tissue. These alterations correlate with changes in the expressions of specific glycosyltransferases. Overexpression of Lewis antigens in some types of cancer might be a significant prognostic factor. Upregulation of Lewis(y), Lewis(b), and other alpha1,2-fucosylated oligosaccharides is linked to an increased tendency to metastasis and resistance to treatment. For example, invasive breast cancer of poor prognosis reveals high expression levels of Lewis(y) and Lewis(b). Lewis(x) is also overexpressed in breast cancer cells. Overexpression of Lewis(a) also occurs in precancerous states of stomach tissue. Upregulation of sialyl Lewis(a) correlates with the metastatic potential of colon and pancreatic malignancies and inversely with survival rate of patients. A similar relation was observed between sialyl Lewis(x) overexpression and malignancies of the lungs, prostate, urinary bladder, stomach, breast, kidney, and liver. Some of the Lewis antigens are ligands of specific receptors and adhesion molecules. For example, Lewis(x) is recognized by scavenger receptor C-type lectin (SRCL), which belongs to the group of innate immunity receptors. Sialyl Lewis(a) and sialyl Lewis(x) specifically interact with E- and P-selectins, which are key molecules in leukocyte rolling process. Ongoing research shows an increasing number of potential therapeutic applications related to the upregulation of Lewis antigens.

Eph receptors are the largest known subfamily of receptor tyrosine kinases. They interact with membrane-bound proteins called ephrins. Recently, an increasing body of evidence shows that ephrins and Eph receptors are involved in pathological processes such as carcinogenesis. Their upregulation in various types of tumors has been demonstrated, highlighting the correlation between this phenomenon and enhanced tumor progression. An exponentially growing interest in their function has resulted in a considerably advanced understanding of the role of ephrins in regulation of cell motility. This is relevant, since active migration is one of the critical cell feature in tumor invasion and metastasis. Here, we summarize recent reports concerning mechanisms of Eph/ephrin signaling and its role in tumour cell migration. Ephrins can regulate cell migration directly, by activation of cytoskeleton rearrangement, or indirectly by changes in cell-cell or cell-ECM adhesion. The relevance of these processes in tumor invasion together with the involvement of ephrins in tumor angiogenesis creates Eph/ephrins pathway as a novel target for cancer treatment.

In response to long term (at least 1-3 h) irradiance changes the responses are elicited at the level of structure and function of photosynthetic apparatus of plants which are thought to be aimed to keep the balance between the level of excitation energy funneled to the reaction centers of the photosystems by energetic antennae and the utilization of this energy in the form of photosynthetic electron transfer and dark reactions. At high vs medium irradiances the rate of excitation energy transfer via LHCII is reduced while the rate of electron flow and photosynthetic dark reactions is increased. The reaction at LHCII level stems from the reduction of its pool per PSII reaction center and the regulatory events comprise changes in the expression of LHCII apoproteins and/or chi b biosynthesis. The basis for higher electron flow capabilities lies in significant increases in the content of some electron carriers and the catalytic activity of ATP synthase. The upregulation of photosynthetic dark reaction in turn is due to the activation of signaling pathways leading to the increase in the pool and catalytic activities of rubisco and other Calvin cycle enzymes.

Mast cells take part in multiple pathological processes, in some of which mast cell accumulation is central to pathogenesis. They are also vital factors in many physiological reactions. Therefore it seems to be of great importance to understand the mechanisms underlying mast cell migration into and within tissues. There are many factors that regulate the migration of mast cell progenitors from the blood into tissues and the migration of mature mast cells within tissues, leading to the rapid local accumulation that occurs in diverse pathological conditions. Without any doubt, cell-surface adhesion molecules are central to the migratory process, as they facilitate the binding of cells to extracellular matrix (ECM) proteins. Immature and mature mast cells express different adhesion molecules, especially integrins, that are involved in mast cell adhesion to such ECM proteins as laminin, fibronectin, vitronectin, and collagens. The expression of adhesion molecules alters during mast cell development and maturation. What is more, mast cell adhesion molecule expression and mast cell adhesion to ECM proteins may be regulated by some cytokines.

Unlabelled: Serotonin (5-HT) is among other factors involved in gastrointestinal motility, secretion and visceral sensation. Available data suggest that secretion and metabolism of 5-HT may be disturbed in irritable bowel syndrome (IBS). Interpretation of these observations have been hampered by the variable methodology used and small numbers of patients involved in the previous studies. Aim of this study was to measure serum 5-TH concentration under fasting condition in patients with irritable bowel syndrome (IBS), compared with controls (K). The metabolite of serotonine--5-hydroxyindole acetic acid (5-HIAA) in urine was also assessed., Methods: 71 subjects, aged 19-50 years were included in this study. Three groups were distinguished: group I (n=25)--healthy volunteers, group II (n=23)--patients with constipation predominant (IBS-C), group Ill (n=23)--subjects with diarrhea predominant irritable bowel syndrome (IBS-D). IBS was diagnosed according to Rome Ill Criteria. On the day of the experiment, patients received a standard meal (Nutridrink 6 x 300 kcal) and blood samples were collected during fasting. 5-HIAA concentration was determined in 24-hour urine collection. Concentration of 5-HT and 5-HIAA was measured by immunoenzyme ELISA method employing standard kits IBL nr RE59121 i RE59131 and Labsystems Multiscan detector., Results: The average serotonin concentration during fasting was found in group I--156.67 +/- 49.12 ng/ml, in group II--221.73 +/- 91.56 ng/ml (p < 0.05), in group III--3.50 +/- 1.71 mg/24h. 5- HIAA concentration in urine was decreased in group Ill--3.50 +/- 1.71 mg/24 hrs (p < 0.05) and group II--4.37 +/- 2.95 mg/24 hrs compared with healthy volunteers--5.65 +/- 2.31 mg/24 hrs., Conclusion: (1) Serotonin concentration is increased in C-IBS and D-IBS patients. (2) Urine 5-hydroxyindole acetic acid excretion is decreased in IBS-subjects. (3) Disturbed metabolism of serotonin probably may play role in pathogenesis of functional bowel diseases.

Aim: The evaluation of serum ICAM, VCAM, endothelin-1 (Et-1), TNF-alpha and its soluble receptor levels and the secretion of nitric oxide in postmenopausal women with hypercholesterolemia., Patients: 26 postmenopausal patients who neither received hormonal therapy nor cholesterol lowering treatment. Group A consisted of 16 women with high serum total cholesterol and group B of 10 women with normal cholesterol level., Methods: Basic fasting serum FSH, 17beta-estradiol, as well as total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides levels were evaluated. Standard exercise test was carried out according to Bruce protocol. Blood samples were taken thrice (prior to, at peak exercise, 15th min of recovery) during the test to evaluate the serum levels of ICAM, VCAM, ET-1, TNF-alpha and its soluble receptors as well as secretion of nitric oxide., Results: In group A--sVCAM (660.0 +/- 106.4 mg/l versus 518.6 +/- 65.4 mg/l; p < 0.05) and TNF-alpha serum levels (2.2 +/- 1.0 ng/l versus 1.2 +/- 0.4 ng/l; p < 0.05) at peak exercise were higher in group A compared to group B. There was a tendency (p > 0.05) of higher ET-1 plasma levels in group A., Conclusion: Serum levels of adhesion molecules and inflammatory mediators were higher during physical exercise in postmenopausal women with atherosclerosis risk factors.

The aim of this study was the estimation of L-selectin expression on PMN and concentration of sL-selectin in patients serum with chronic myelogenic leukemia. The results indicate the increased expression of L-selectin on isolated neutrophils from peripheral blood of patients with chronic myelogenic leukemia. A concentration of sL-selectin was also increased in patients serum with chronic myelogenic leukemia. High concentration of L-selectin on PMN makes binding neoplastic cells easier. Increased level of sL-selectin might activate of the adhesion process in patients with chronic myelogenic leukemia. High expression of L-selectin on PMN may be a response to higher levels of TNF-alpha in serum blood patients with chronic myelogenic leukemia.

Purpose: The aim of this study was to investigate the expression of HLA-DR antigen on conjunctival epithelial cells from patients with dry eye., Material and Methods: Ophthalmic examination and dry eye diagnostic tests were performed. Impression cytology specimens were collected in thirty patients with dry eye and in thirty people of control group. Conjunctival epithelial cells were processed for flow cytometry, by using monoclonal antibodies to HLA-DR., Results: A significant increase of HLA-DR expression on epithelial cells was found in patients with dry eye compared with normal eyes. We also found positive correlation of increased expression HLA-DR with ocular complaints and diagnostic tests for dry eye such as Schirmer test, FBUT and lissamine green staining., Conclusions: These results confirm the presence of immunological processes in the pathogenesis of dry eye syndrome. Increased expression of HLA-DR antigen positively correlates with the parameters of dry eye diagnostic tests. HLA-DR measurement might be a useful method for monitoring inflammatory conjunctival changes in this disorder.

Adipose tissue generates many bioactive substances, which may exert autocrine, paracrine and endocrine effects. Recent studies have revealed, that one of these substances is nitric oxide. There are observed increased expressions of synthases NO (eNOS and iNOS) in adipose tissue in obesity. It seems that these increased expression NOS is reflected by increased serum concentration of NO in obese subjects. The review of the current literature on role of nitric oxide in physiology and pathology metabolism is presented in this paper.

Unlabelled: Cyclosporine A (CsA) is a potent immunosuppressant introduced to the treatment of idiopathic nephrotic syndrome (INS) in children. Besides beneficial effects on the clinical course of the disease, this drug may also influence the function of first line defence cells. The aim of the study was to assess the granulocyte generation of reactive oxygen intermediates (ROI) in children suffering from idiopathic nephrotic syndrome treated with cyclosporine A., Material and Methods: The study group consisted of 10 children (aged 4-18 yrs.) in at least 2 month-long remission of steroid-dependent INS treated with CsA (group A), 16 children in long-term remission (at least 18 months without treatment) of INS (group B). Twelve healthy age-matched children (group C) constituted control group. ROI generation was measured by the luminol-dependent chemiluminescence of whole blood using MLX Microtiter Plate Luminometer, Dynex. The following parameters were evaluated: spontaneous chemiluminescence, chemiluminescence induced by formyl-Met-Leu-Phe (fMLP), opsonized zymosan (OZ) and phorbol acetate (PMA)., Results: The primary results were corrected according to the absolute number of neutrophils and hemoglobin concentration. Final results were presented as relative luminescence units RLUmax (Relative Light Units Max). In children treated with CsA we found significantly increased spontaneous, fLMP and OZ stimulated chemiluminescence activity compared to patients from group C. Chemiluminescence tests conducted in the long-term remission of INS gave similar results with respect to neutrophil reactivity. CONCLUSION. The neutrophil function measured by spontaneous and receptor-dependent oxidative burst in children with either cyclosporine-induced or long-term treatment-free remission seems to be upregulated. The potential clinical implications of these observations remain to be established.

Overexpression of the Erb B-2 receptor plays an important role in the pathogenesis of breast cancer. It results in the formation of heterodimers consisting of Erb-B2/Erb B-3 receptors which have an ability to produce stable and external factors independent mitotic stimuli. Together with an autocrine stimulation of neoplastic cell proliferation by heregulin and cyclooxygenase 2 activation it is a significant factor in carcinogenesis. Overexpression of Erb B-2 seems to be an independent negative prognostic factor in breast cancer. Its predictive value is not clear-cut. It is suggested that breast cancer showing Erb B-2 overexpression is more sensitive to treatment with anthracyclines and less to CMF. The anti-Erb B-2 monoclonal antibody (trastuzumab) is used in treatment of metastatic breast cancer both as a single drug and in combination with chemotherapy.

The aim of this study was to estimation of LFA-1 expression on PMN and concentration of sICAM-1 in serum patients with chronic myelogenic leukemia. The results indicate on increased expression of LFA-1 on isolated neutrophils from peripheral blood of patients with chronic myelogenic leukemia. A concentration of sICAM was increased in serum patients with chronic myelogenic leukemia either. High expression of adhesion molecules can make easier binding neoplasmatic cells to LFA-1 and facilitate their migration to other tissues (distant metastases). On the other hand, soluble forms of ICAM can block connection neoplasmatic cells to membrane forms of adhesion molecules. Probably, the balance between membrane--bound and soluble forms of adhesion molecules is responsible for malignancy progression.

Objectives: Most endometrioid, well differentiated cancers are positive for ER and PgR., Materials and Methods: By using specific monoclonal antiER, PgR, p53 and hsp 90 antibodies, immunohistochemical reaction was used to study paraffin-embedded specimens from 53 patients with primary endometrioid and clear cell cancers., Results: Most carcinomas with p53 overexpression showed no reactivities of ER and PgR., Conclusions: Presence of p53 and absence of steroid hormone receptors suggest a poor clinical prognosis for patients with endometrioid and clear cell cancers.

Nitric oxide (NO) is highly active molecule playing a key role in physiological as well as pathological processes in the organism. Asthmatic patients show an increased expression of inducible nitric oxide synthase (iNOS) in airway epithelial cells and an increased level of NO in exhaled air. Exhaled NO increases during exacerbation and decreases with recovery in patients with asthma. The role of excessively produced NO in the pathogenesis of asthma is under active investigation. Determination of airway production of NO may be an important biomarker of inflammation for monitoring anti-inflammatory therapy.

The development and progression of astrocytic tumours is associated with acquisition and accumulation of genetic alternations. Loss of heterozygosity (LOH) on chromosome 17p., p53 mutations and overexpression of the platelet-derived growth factor (PDGF) receptor (chromosome 22q), are the most common detectable changes in astrocytomas (WHO grade II). Anaplastic astrocytomas (WHO grade III) involve LOH on chromosome 19q, deletion of p16 tumor suppressor gene on chromosome 9p and disturbed expression of gene RB on chromosome 13q. LOH on chromosome 10 is restricted largely to glioblastomas (WHO grade IV). This tumour also is characterized by amplification and/or overexpression of gene coding Epidermal Growth Factor Receptor (EGFR) on chromosome 7p. There is growing evidence that two genes encoding triiodothyronine receptors TR alpha [17q21] and TR beta [3p21-p25]) belong also to the group of genes involved in tumorigenesis. Mutations of these genes as well as markedly disturbed expression and function of the encoded proteins were found in tumour tissue. This is supported by facts. that T3 via TRs regulate proliferation, growth, differentiation and apoptosis, the processes that are deeply disturbed in tumour tissue. TRs affects also the action of certain protooncogenes (Mdm2) and tumor suppressors (p53, Rb).

Two cases of invasive carcinoma developing in extragonadal endometriosis are presented. Each case had a different clinical course. In addition to routine histopathologic studies immunohistochemical studies to assess the expression of cytoceratin and glycoprotein CD-44 were performed. In both cases CK-7 expression was higher in malignancy then in the endometrioid tissue. Very high expression of CD-44 protein (marker of metastatic potential) was found in patients with poor progress of the disease.

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

Using sensitive techniques such as reverse transcription polymerase chain reaction (RT-PCR) the expression of WT1 gene in acute lymphoblastic leukemias (ALL) is indicated. High level of mRNA WT1 was only observed in ALL cases with leukemic cells characterized by P53- and MDM2-positive staining in cytometric analysis. The overexpression of P53 protein has not been induced by P53 gene abnormalities and MDM2 protein synthesis was independent from respective gene amplification. The data suggest that WT1 may play a distinct role in the pathophysiology of acute leukemias. It can regulate the function of the main oncoprotein network factors--P53 and MDM2 proteins. There was concluded that the most important mechanism of tissue P53-immunopositivity was connected with the P53 interactions with other oncoproteins, especially with MDM2 and WT1. They have caused different effects in particular cases and several phenotypes of leukemic cells were described. However, the negative tissue staining with anti-P53 monoclonal antibodies can not be evidence of the proper P53 protein function. The immunohistochemical estimations of the P53 level in the cells are insufficient for diagnostic and clinical evaluations. Molecular analyses of P53 and MDM2 genes, as well the WT1 gene transcription, are necessary for the proper characterisation of functional and structural status of P53.

Bcl-2 gene is an important factor in regulation of apoptosis as an inhibitor of this process. Its increased expression is observed in numerous neoplasms, what points out on importance of this gene in the process of oncogenesis. The aim of this paper was to assess the expression of bcl-2 gene in the cells of the glia-derived tumours of the brain. The method of Chomczyński and Sacchi with guanidine tiocyanate was applied to isolate a whole cellular RNA. Expression of bcl-2 gene was measured with a reverse transcription method by a synthesis of cDNA and amplification of gene fragment with specific oligonucleotides in polymerase chain reaction (RT-PCR). The expression of bcl-2 gene was found in cells of all examined glial tumours at the level of transcript. We carried out the discussion of the results and an attempt to explain the importance of bcl-2 gene expression of these neoplasms.

In tumor tissue obtained from a group of 21 patients treated surgically for laryngeal carcinoma, the expression of Fas, Fas-L, CD3, TCR zeta chain and Bcl-2 were estimated. It has been shown that tumor often express: Fas-L, Fas, Bcl-2, the molecules which may influence increased tumor survival. On the other hand lack of MHC class I antigen expression on tumor cells frequently has been observed. As it is known, such tumor cells can not be recognized by cytotoxic T lymphocytes. Frequently observed decreased expression of TCR zeta chain and high level of apoptosis among T cells present in tumor microenvironment seems to depend on direct interactions with molecules expressed by tumor. Understanding of these interactions may be of great importance in evaluation of tumor aggressiveness, patients follow up and the approach to treatment.

The Na+/I- symporter (NIS) is the plasma membrane protein that catalyzes the accumulation of iodine into thyroid cells against an electrochemical gradient. This iodine uptake is the first step in thyroid hormone biogenesis which is stimulated by TSH--the main hormone regulating thyroid--specific functions. This process requires energy from the action of Na+/K+ ATP-ase. TSH upregulates NIS gene expression, and this induction can be modulated by cytokines. Analysis of the distribution of NIS mRNA demonstrated variable levels of NIS transcription in different tissue samples. Increased NIS expression has been found in autonomous adenoma and Graves' disease, decreased levels of NIS protein and/or mRNA NIS were observed in Hashimoto's disease, scintigraphically cold nodules and most thyroid cancers. NIS mutation has been found in congenital hypothyroidism. Potential defects in the NIS gene are currently under investigation in various thyroid diseases.

Stimulation of epidermal growth factor receptor (EGFR) leads to cell proliferation and plays an important role in cancerogenesis. It seems that these effects are a consequence of triggering of various signal transduction pathways involving PI-3K and MAP kinase activation. Surprisingly, under certain circumstances stimulation of EGFR may also result in cell growth arrest and apoptosis induction. It is possible that anti-proliferative effect of EGF depends on STAT protein activation. It has been reported, that STAT upregulates expression of cyclin-dependent kinase inhibitor, which blocks the cell cycle. Additionally, STAT may increase caspase 1 (ICE) expression, which seems to be necessary for apoptosis induced by EGF. Intracellular mechanisms involved in EGFR proapoptotic activity still remains poorly understood and, because of their potential clinical significance, require further investigation.

Both subunits of IL-6 membrane--associated receptor, IL-6R and gp130 can exhibit in a soluble forms--sIL-6R and sgp130 respectively. Soluble IL-6 receptor (sIL-6R) can bind IL-6 and mediate IL-6 function through association with gp130 which is the signal transducing protein. In contrast to other receptors, sIL-6R has a potential to enhance the IL-6 biological function. sIL-6R and sgp130 were found in appreciable amounts in body fluids, although the exact cellular source and function of these proteins are not completely clear.

The authors have reviewed the bibliography on the behaviour of epidermis lipids in the course of psoriasis. In individual papers the researchers have reported numerous irregularities concerning epidermal lipids in psoriasis.