Is M235T polymorphism of the angiotensinogen gene involved in the development of endometriosis?

OBJECTIVES: The aim of the study was to analyze the M235T polymorphism of the angiotensinogen (AGT) gene in women with endometriosis and to identify correlations between identified genotypes and the disease progression, its stage and clinical course as well as to evaluate the prognostic value of the investigated polymorphism in patients with endometriosis treated for infertility. MATERIAL AND METHODS: The study group consisted of 241 women with minimal to severe stage of endometriosis, the control group (without endometriosis) - 127. The molecular analysis was performed by PCR-RFLP technique. RESULTS: The analysis of the frequency of genotypes and alleles of M235T polymorphism showed no significant differences between the study and the control groups and between the severity grades of the disease (p > 0.05). No such differences were reported in the case of different localizations of the disease lesions, either. Evaluation of the correlations related to pain accompanying endometriosis did not demonstrate association with any genotypes of the analyzed AGT gene poly-morphism. Comparison of the results obtained in the group in which infertility treatment was successful (n = 54) and in those who failed to conceive (n = 73) did not show the correlation between the investigated polymorphism and the effect of infertility treatment. CONCLUSIONS: M235T polymorphism of the AGT gene seems unrelated to the development or the clinical course of en-dometriosis. No prognostic value has been found of the investigated polymorphism in predicting the effects of infertility treatment in women with endometriosis.

[The effect of solar ultraviolet radiation (UVR) on induction of skin cancers]. / Wplyw slonecznego promieniowania ultrafioletowego (UV) na powstawanie raków skóry.

Ultraviolet radiation is a physical mutagenic and cancerogenic factor. About 95% of ultraviolet A (UVA) (320-400 nm) and 5% of UVB (280-320 nm) reach the Earth's surface. Melanin is a natural skin protective factor against UV radiation. Skin cancers associated with long-term exposure to UV radiation are: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). The high risk of BCC development is related to acute and repeated exposure to UV causing sunburn. Molecular studies of BBC demonstrated disorders in sonic hedgehog (SHH) cell signaling regulation pathway, associated with the suppressor protein patched homolog 1 gene (PTCH1) mutations. The risk of the BCC development is related to the polymorphism of melanokortin-1 receptor gene (MC1R). Tumor P53 gene mutations observed in BCC cells has been classified as secondary genetic changes. In SCC cells UV-induced mutations were mostly related to P53 gene. Increased expression of cyclooxigenase- 2 gene (COX-2) plays a significant role in the development of SCC. Other pathogenetic factors include intensification of the synthesis of pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1ß and IL-6). Currently, the role of UVB has been recognized in the pathogenesis of CMM. In CMM cells the following gene mutations were noted: cyclindependent kinase inhibitor 2A INK4A (p16INK4A), cyclin-dependent kinase 4 (CDK4), Ras, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and proto-oncogene B-Raf (BRAF). The BRAF gene mutations were observed in ~50% of CMM cases. Mutations of P53 gene are not characteristic of CMM cells. Med Pr 2016;67(2):255-266.

Elevated frequencies of micronuclei in pregnant women with type 1 diabetes mellitus and in their newborns.

Pregestational diabetes mellitus (type 1 and type 2) affects about 1% of the obstetric population. In diabetes, persistent hyperglycemia can be a source of DNA damage via overproduction of reactive oxygen species (ROS). Using the cytokinesis-block micronucleus (CBMN) test, we measured the frequencies of micronuclei (MN) per 1000 binucleated (BN) cells in pregnant women (mothers) with type 1 diabetes mellitus (T1DM) and in their newborns. Peripheral blood lymphocytes were collected from 17 pregnant women with T1DM and cord-blood lymphocytes from their 17 newborns. The control group included 40 pregnant women (mothers) without diabetes mellitus (DM) and their 40 newborns. In the group of pregnant women with T1DM, the mean number of MN per 1000 BN cells was 2.35 (±1.07), significantly (p<0.001) higher than in the control group of pregnant women (0.86±0.90). The frequency value in the group of newborns of T1DM mothers was 1.42 (±0.60), significantly (p<0.05) higher than in the corresponding control group (0.67±0.79). The value in the group of mothers with T1DM was significantly (p<0.05) higher than in their newborns. Comparing mothers without DM with their newborns, no significant frequency differences were observed. No significant correlations were observed between MN frequencies in mothers with T1DM and either the frequencies in their newborns, the duration of diabetes, or HbA1C levels. Our results indicate that T1DM is accompanied by increased frequencies of MN in pregnant women and their newborns.

Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in cultured cord-blood lymphocytes of newborns of women treated for epilepsy during pregnancy.

Epidemiological data indicate that pregnancies of epileptic women constitute about 1% of all pregnancies. Newborns of mothers exposed to anti-epileptic drugs (AEDs) are at increased risk for major congenital malformations, cognitive impairment and fetal death. Cord-blood lymphocytes of the newborns whose mothers received long-term AEDs therapy during pregnancy were used in this study. There were 37 newborns (Group A), divided into two subgroups, i.e. from mothers receiving mono-therapy (A1) and from those receiving poly-therapy (A2). The major drugs given to the pregnant women with epilepsy in mono-therapy were valproic acid (VPA) and carbamazepine (CBZ) analogues. In poly-therapy, besides VPA and CBZ derivatives also phenyltriazine, sulphanamide, benzodiazepines and gamma-aminobutyric acid (GABA) derivatives were administered. Three kinds of in vitro cytogenetic test were applied: the chromosome aberration (CA) assay, the sister chromatid exchange (SCE) assay, and the cytokinesis-block micronucleus assay (CBMN). In addition, the mitotic index (MI), the replication index (RI) and the nuclear division index (NDI) were determined. The mean number of CA/cell (excluding gaps) for group A did not differ statistically significantly from the negative controls (p>0.1), nor did the mean MI value (p>0.1). In group A, the mean number of SCE/cell was statistically significantly higher compared with the negative control (p<0.05). The mean RI value for group A did not demonstrate statistically significant differences (p>0.1). The mean MN number for group A was higher than in the negative control, but this difference was on the border of statistical significance (p=0.07). The value of NDI for group A did not differ significantly from the value in the negative control (p>0.1). The anti-epileptic drugs given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes. These drugs did not exert a cytotoxic effect, neither did they inhibit the cell-division kinetics of cord-blood lymphocytes.

[Poisoning with selected mushrooms with neurotropic and hallucinogenic effect]. / Zatrucia wybranymi grzybami o dzialaniu neurotropowym i halucynogennym.

Picking mushrooms, especially in summer and autumn, is still very popular in Poland. Despite raising awareness of poisonous mushrooms in the Polish society, year after year hospitals treat many patients diagnosed with poisoning with the most common toxic species of mushroom found in our country. Furthermore, growing interest in hallucinogenic mushrooms among young people has become a serious medical problem of our time. Websites make it incredibly easy for people to obtain information on the morphology and appearance of mushrooms with psychoactive properties, which leads inexperienced pickers to misidentification, resulting frequently in a fatal outcome. The article explores the subject of poisoning with the most common mushrooms with neurotropic effects, these are: Amanita muscaria, Amanita pantherina, Inocybe rubescens, Clitocybe dealbata, Clitocybe rivulosa and Psilocybe semilanceata. Toxins found in these species show symptoms that affect the central nervous system, parasympathetic system as well as the gastro-intestinal system. The effects of poisoning in the mushroom species mentioned above are mild in general, liver and kidney damage occur rarely, but the symptoms depend on both the dosage of the consumed toxins and individual susceptibility. In most cases the treatment is of symptomatic nature. There is no specific treatment. Medical procedures mainly involve induced gastrolavage--stomach pumping (providing that the patient is conscious), prescription of active carbon as well as replacement of lost body fluids and electrolytes. If the muscarinic symptoms prevail it is generally advised to dose atropine. Patients showing the signs of hyperactivity receive tranquilizers or narcoleptics to eliminate psychotic symptoms.

Experimental and Numerical Investigation of Mechanical Properties of Lightweight Concretes (LWCs) with Various Aggregates.

High requirements for the properties of construction materials and activities directed at environment protection are reasons to look for new solutions in concrete technology. This research was directed at solutions affecting the reduction of energy consumption and CO2 emissions. The use of lightweight concretes (LWCs) allows one to meet both conditions at the same time. The purpose of the research presented in this paper was to investigate the abilities of using lightweight aggregates (LWAs) of the following types: 2 and 4 mm granulated expanded glass aggregate (GEGA) as ingredients with excellent insulating properties and 8 mm granulated fly ash aggregate (GAA) as an ingredient with a relatively high resistance to crushing. The influence of the percentage participation of each aggregate in all LWCs was variable and amounted to 0%, 25%, 50%, 75%, and 100%. A series of 15 LWC mixes were prepared for various LWA participations and for a constant water-cement ratio (w/c = 0.5). Concrete tests were carried out for the following criteria: density, porosity, compressive strength, and the modulus of elasticity. In order to fully analyze fracture processes in LWCs with the participation of GEGA and GAA and to assess the correctness of the results obtained during the experiments, numerical models that corresponded to both geometrical and load diagrams of elements under research were created. The numerical analyses of the LWCs were conducted by means of the conventional finite element method (FEM).

[Poisonings with Amanita phalloides]. / Zatrucia muchomorem sromotnikowym (Amanita phalloides).

Amanita phalloides is the most dangerous, poisonous mushroom species in our climatic conditions. It is the cause of 90-95% of all deaths due to mushroom poisoning, a-Amanitin, a polymerase RNA II inhibitor, is mainly responsible for the Amanita phalloides toxic property. Inhibition of polymerase RNA II functioning in a transcription process is connected with inhibition biosynthesis of structural and enzymatic proteins in cells. A lethal dose of a-amanitin is 0.1 mg/kg b.w. for humans. One of the medical problems in Amanita phalloides poisonings is a relatively prolonged latency period (8-24 h) from mushroom ingestion, at the same time the cytotropic action of absorbed toxins is revealed. In severe cases, multi organ failure, renal and hepatitis failure can occur. Deaths in a-amanitin poising cases follows between 6-16 days after intoxication. Mortality in this group of patients is still high and amounts to approximately 20-30% in adults and exceeds 50% in children. If mushroom poisoning occurs, it is best treated with pharmacological agents, extracorporeal methods for toxin removal and liver transplantation. Recent high expectations concerning liver albumin dialysis (based on MARS) should support liver regeneration and will also help with possible liver transplantation. In a medical community it is generally believed that every suspected Amanita phalloides poisoning should be referred to a specialized health center.

Angiotensinogen gene T174M polymorphism is related to Hashimoto's thyroiditis.

OBJECTIVES: The Hashimoto thyroiditis is found to be Th1-related autoimmunity. Recently, it has been proved that the renin-angiotensin-aldosterone system (RAAS) may be involved in promoting Th1-mediated autoimmune diseases. However, the role of RAAS in HT pathogenesis remains still unknown. The aim of this study was to determine whether the polymorphisms of ACE, AGTR1 and AGT genes are associated with HT. MATERIAL AND METHODS: Polymerase Chain Reaction (PCR) was performed to determine ACE I/D, AGTR1 A1166C and AGT T174M polymorphisms and next chi-square test was used to compare allele frequencies of genes between HT patients (n=53) and the control group (n=31). RESULTS: TM genotype of AGT gene has been more often presented in HT patients (p <0.05). No others statistically significant differences were found in the distribution of I/D ACE and A1166C, AGTR1 genes polymorphisms between studied groups. CONCLUSION: Our study has examined for the first time the association of genes related to RAAS with autoimmune thyroid disease and results suggest that AGT TM genotype individuals might be at higher risk of HT. Although in the present study we have not found any association between increased activation of RAAS and the risk of HT, still this issue seems to be interesting and worthy further research, considering patients with thyroid cancers.

The effect of antiepileptic drugs administered in pregnancy on micronucleus frequency in cord blood lymphocytes.

OBJECTIVES: Epidemiological data indicate that the pregnancies of epileptic women constitute about 1% of all pregnancies. A large group of antiepileptic drugs (AEDs) applied in long-term monotherapy or polytherapy produce toxic metabolites as well as free radicals and reactive oxygen species. The aim of this study was to assess the potential genotoxic effect of AED therapy in pregnancy on DNA structure of umbilical cord blood lymphocytes. MATERIAL AND METHODS: The study group were 30 newborns (14 males and 16 females) of mothers receiving long-term AED therapy during pregnancy. The AED considered were carbamazepine, valproic acid, phenyltriazine, benzodiazepine, gamma-aminobutyric acid and sulfonamide analogues. The controls were infants born to mothers not exposed to any medication in pregnancy (n = 20). Positive controls were the same infants, but in this case Nitrogranulogen (Sigma) was added to the collected cord blood samples (n = 11). Micronucleus (MN) assay was used as an indicator of chromosome damage. The frequency (%) of MN/1000 binucleated cells and the nuclear division index (NDI) were calculated. RESULTS: Mean MN frequency and NDI were respectively 0.110 (+/-0.152), 1.592 (+/-0.206) in the study group and 0.050 (+/-0.061), 1.628 (+/-0.178) in the controls (statistically non-significant difference, p > 0.1). CONCLUSION: The findings did not reveal any genotoxic effect or inhibition of nuclear division in cord blood lymphocytes by AED metabolites. This was reflected by the absence of significant between-group differences in the mean MN frequency and NDI.

[The metabolic syndrome. Part I: definitions and diagnostic criteria for its identification. Epidemiology and relationship with cardiovascular and type 2 diabetes risk]. / Zespól metaboliczny. Czesc I: definicje i kryteria rozpoznawania zespolu metabolicznego. Epidemiologia oraz zwiazek z ryzykiem chorób sercowo-naczyniowych i cukrzycy typu 2.

The term metabolic syndrome (MS) refers to a clustering of risk factors of metabolic origin that promote the development of cardiovascular disease and type 2 diabetes. Metabolic syndrome includes such pathological factors as insulin resistance, hyperinsulinemia, abdominal obesity, impaired glucose tolerance, type 2 diabetes, microalbuminuria, high level of triglycerides, low level of HDL cholesterol, elevated blood pressure, and proinflammatory and prothrombotic state. Several organizations have recommended clinical criteria for the diagnosis of metabolic syndrome. The most widely accepted were the worked out by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), and the National Cholesterol Education Program--Third Adult Treatment Panel (NCEP-ATP III). In 2005, IDF experts proposed a universally accepted diagnostic tool that is easy to use in clinical practice and does not rely on measurements available only in research settings. All groups agreed on the core components of the metabolic syndrome: obesity, insulin resistance, dyslipidemia, and hypertension. Their criteria are similar in many aspects, but they also reveal fundamental differences in their positioning of the predominant causes of the syndrome. This study provides a brief overview of current definitions of metabolic syndrome, with particular reference to the differences between them, and presents critical remarks on the concept of metabolic syndrome and its usefulness. It also presents epidemiological data which consider metabolic syndrome and its association with increased risk of cardiovascular disease and type 2 diabetes.

[The metabolic syndrome. Part II: its mechanisms of development and its complications]. / Zespól metaboliczny. Czesc II: patogeneza zespolu metabolicznego i jego powiklan

The metabolic syndrome is a cluster of interrelated metabolic factors such as insulin resistance, hyperinsulinemia, abdominal obesity, impaired glucose tolerance, dyslipidemia, hypertension, and a proinflammatory and prothrombotic state. It is a common cause of the development of atherosclerotic vascular disease and type 2 diabetes. Genetic predisposition and environmental factors such as physical inactivity and increased caloric intake are responsible for the predisposition to metabolic syndrome. Available studies on the pathogenesis of metabolic syndrome are discrepant. Insulin resistance and abdominal obesity are the dominant causes of metabolic syndrome. Increased visceral adipose tissue mass and its proinflammatory activity are thought to underlie all the changes observed in metabolic syndrome. Adipose tissue is a dynamic endocrine and paracrine organ that produces and secretes inflammatory factors called adipokines, which link obesity, insulin resistance, atherosclerosis, and type 2 diabetes. Recent data suggest that oxidative stress is a primary pathogenic mechanism leading to the development of insulin resistance associated with over-nutrition. In this study the authors analyze the association between abdominal obesity, hyperinsulinemia, and insulin resistance and show some pathogenic mechanisms which may be responsible for the proatherogenic action of insulin resistance, hyperinsulinemia, and impaired glucose tolerance. Here the association among the disorders mentioned in the definitions of metabolic syndrome is discussed in more detail and it is shown that their clustering is not accidental in patients with insulin resistance. The role of adipose tissue in the development of insulin resistance and metabolic syndrome leading to overt cardiovascular disease and type 2 diabetes is also described.

[Metabolic syndrome. Part III: its prevention and therapeutic management]. / Zespól metaboliczny. Czesc III: postepowanie prewencyjne i terapeutyczne w zespole metabolicznym.

Metabolic syndrome (MS), which is composed of such factors as hyperinsulinemia, insulin resistance, glucose intolerance, abdominal obesity, arterial hypertension, and dyslipidemia, contributes to accelerated development of atherosclerosis, coronary artery disease, and type 2 diabetes. It has thus become one of the major public-health challenges worldwide. The primary goal of its clinical management is to reduce the risk for cardiovascular diseases related to atherosclerosis, especially myocardial infarction, stroke, and peripheral vascular disease, and to lower the risk for type 2 diabetes. The fi rst stage in its successful preventive management is identification of the population at high risk of developing metabolic syndrome. The therapeutic approach to metabolic syndrome consists fi rst of all of lifestyle modification, i.e. the introduction of a low calorie diet, weight reduction, and regular physical activity. For people at high risk for cardiovascular diseases and type 2 diabetes as well as those with coronary artery disease and/or type 2 diabetes, pharmacological therapy should be considered. Pharmacological management must address the multipathological process of metabolic syndrome, with each component identified and properly treated. Current therapies for metabolic syndrome treat fi rst of all obesity, insulin resistance, dyslipidemia, and hypertension. The pharmacological agents most often suggested are those which increase insulin resistance (metformin and thiazolidinediones). Among the medications used in metabolic syndrome therapy are also fibrates and statins for atherogenic dyslipidemia and those lowering blood pressure, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. This review presents the most important aspects of the prevention and treatment of patients with metabolic syndrome, including new therapeutic strategies.

The influence of a change in the meniscus cross-sectional shape on the medio-lateral translation of the knee joint and meniscal extrusion.

OBJECTIVE: The purpose of this study was to evaluate the influence of a change in the meniscus cross sectional shape on its position and on the biomechanics of a knee joint. METHODS: One main finite element model of a left knee joint was created on the basis of MRI images. The model consisted of bones, articular cartilages, menisci and ligaments. Eight variants of this model with an increased or decreased meniscus height were then prepared. Nonlinear static analyses with a fixed flexion/extension movement for a compressive load of 1000 N were performed. The additional analyses for those models with a constrained medio-lateral relative bone translation allowed for an evaluation of the influence of this translation on a meniscus external shift. RESULTS: It was observed that a decrease in the meniscus height caused a decrease in the contact area, together with a decrease in the contact force between the flattened meniscus and the cartilage. For the models with an increased meniscus height, a maximal value of force acting on the meniscus in a medio-lateral direction was obtained. The results have shown that the meniscus external shift was approximately proportional to the meniscus slope angle, but that relationship was modified by a medio-lateral relative bone translation. It was found that the translation of the femur relative to the tibia may be dependent on the geometry of the menisci. CONCLUSIONS: The results have suggested that a change in the meniscus geometry in the cross sectional plane can considerably affect not only the meniscal external shift, but also the medio-lateral translation of the knee joint as well as the congruency of the knee joint.

Molecular cytogenetic analysis of chromosome aberrations in desmoid tumors.

To date there are only few reports concerning chromosomal changes in desmoid tumors. To extend the knowledge in this field we examined 19 samples from the patients diagnosed with desmoid tumors. In the present study formalin-fixed and paraffin-embedded desmoid tumors were analyzed using fluorescence in situ hybridization (FISH) with a-satellite probes for chromosomes X, Y, 8 and 20. Chromosomal abnormalities were found in 6 cases, both abdominal and extra-abdominal tumors. FISH studies revealed one case of trisomy 8 and trisomy 20. In four patients we have identified monosomy 20. Our findings confirm earlier reports concerning the diversity of chromosomal changes in desmoid tumors and might suggest that both groups of abdominal and extra-abdominal tumors are genuine neoplasms.

[Pathogenesis and genetics of neural tube defects]. / Patogeneza i genetyka wad cewy nerwowej.

After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC).

What is the impact of gestational diabetes mellitus on frequency of structural chromosome aberrations in pregnant women and their offspring?

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance which results in hyperglycemia first diagnosed during pregnancy. It is associated with an increased levels of oxidative stress due to overproduction of reactive oxygen species (ROS). Overproduction of ROS induces protein oxidation, lipid peroxidation and different types of DNA damage. The objective of this study was to determine the frequencies of structural chromosome aberrations (CA) in peripheral blood of pregnant women (mothers) with GDM and in cord blood of their newborns. Peripheral blood lymphocytes were collected from 35 GDM mothers and cord blood lymphocytes from their 35 newborns. The control group included 30 pregnant mothers without diabetes mellitus (DM) and their 30 newborns. CA were evaluated with in vitro chromosome aberration assays. We observed a moderate increase of the mean numbers of structural CA between GDM mothers and their newborns, GDM mothers and mothers without DM, GDM mothers' offspring and the offspring of mothers without DM, mothers without DM and their newborns, but this effect did not reach statistical significance (p>0.1).

Aggressive fibromatosis (desmoid tumors): definition, occurrence, pathology, diagnostic problems, clinical behavior, genetic background.

Aggressive fibromatosis, usually called desmoid tumor develops from muscle connective tissue, fasciae and aponeuroses. This neoplasm is composed of spindle (fibrocyte-like) cells. As regards the site, aggressive fibromatoses can be divided into: extra-abdominal in the area of the shoulder and pelvic girdle or chest and neck wall; abdominal in abdominal wall muscles; intra-abdominal concerning pelvis, mesentery connective tissue or retroperitoneal space. Desmoid tumor is a neoplasm which rarely turns malignant and is non-metastasizing but demonstrates ability to local infiltration into tissue and is characterized by high risk of recurrence (25-65%) after surgical treatment. Desmoid tumor etiology is uncertain. This neoplasm occurs in sporadic (idiopathic) form and is also associated with some familial neoplastic syndromes. Most sporadic cases of aggressive fibromatosis contain a somatic mutation in either the adenomatous polyposis coli (APC) or beta-catenin genes. Sporadic tumors are more frequent in women than in men from 2 : 1 to 5 : 1. In about 10-15 per cent of patients with familial adenomatous polyposis (FAP), aggressive fibromatosis is a parenteral manifestation of this familial syndrome conditioned by APC gene mutation. Abdomen injury--most frequently due to surgery is said to play an important role in the initiation of fibrous tissue proliferative process in the cases of abdominal and intra abdominal forms. High cells growth potential with relatively high local malignancy is observed in about 10% of cases with sporadic tumors as well as in those FAP-associated.

Analysis of TGF-beta protein expression in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis, usually termed desmoid tumor, develops from muscle connective tissue, fasciae and aponeuroses. Aggressive fibromatosis located in various parts of the body demonstrates differentiated biological behavior. Abnormalities in TGF-beta expression are very common in many disease processes, including neoplasms. Immunohistochemical analysis employing a monoclonal antibody against TGF-beta was performed on archival material, consisting of 38 cases of aggressive fibromatosis, among which 23 represented abdominal, 11 extra-abdominal and 4 intra-abdominal localizations. The sections for immunohistochemical study were stained using the streptavidin-biotin (ABC) method. The average percentage of cells positively stained for TGF-beta protein was 40.2% in the group of extra-abdominal, 58.5% in the group of abdominal and 72.8% in the group of intra-abdominal localizations. There were significant differences observed between the analyzed groups of desmoid tumor (p<0.05). A positive cytoplasmic reaction for TGF-beta was noted in 65.8% (25/38) of the aggressive fibromatoses. Overexpression of TGF-beta protein was noted in 39.5% (15/38) of the aggressive fibromatoses. High expression noticed in desmoid fibroblasts might indicate that this protein plays a crucial role in the development of aggressive fibromatosis.

Analysis of p27KIP1 protein and Ki-67 expression in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis (desmoid tumor) is an uncommon locally invasive non-metastasizing neoplasm lesion. Desmoid tumor consists of fibroblasts, miofibroblasts and a significant amount of extracellular matrix. p27KIP1 (p27) protein is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family that regulates progression through the cell cycle. In various human neoplasms the decreased level of p27 was observed. There were analysed 42 specimens of aggressive fibromatosis, in which there were 24 abdominal and 18 extra-abdominal cases. There was performed immunohistochemical analysis employing a monoclonal antibody against p27 protein and Ki-67 (Novocastra, UK). The sections for immunohistochemical study were stained using the streptavidin - biotin method. The average percentage of cells stained positively for all cases for p27 and Ki-67 was 22.1% (SD=29.2) and 6.0% (SD=8.8) respectively. There was no statistically significant difference between Ki-67 or p27 expression in abdominal and extra-abdominal location. Analysis of p27 and Ki-67 expression levels might indicate that low proliferating activity of desmoid fibroblasts is connected with another mechanism than the one, in which p27 takes part.

Analysis of cyclin D1 and retinoblastoma protein immunoreactivity in follicular thyroid tumors.

Protein products of cyclin D1 and retinoblastoma (Rb) genes play crucial roles in regulation of G1/S transition in the cell cycle. In this study we analyzed, using immunohistochemical methods, the expression of cyclin D1 and Rb proteins in material from medical archives (12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 nodular goiter cases). A positive nuclear reaction for cyclin D1 was observed in 83.3% (10/12) of the follicular carcinomas, in 96.5% (55/57) of the follicular adenomas and in 23.5% (4/17) of nodular goiters. Overexpression of cyclin Dl (more than 50% of positively staining cells) was noted in 25% (3/12) of the follicular carcinomas and in 22.8% (13/57) of the follicular adenomas. No overexpression of cyclin D1 was noted among nodular goiters. The number of carcinoma cases with cyclin D1 overexpression did not differ statistically in any significant way from the follicular adenoma group (p = 1.000). A positive nuclear reaction for Rb protein was noted in 100% of the follicular carcinomas (12/12), in 96.5% of the follicular adenomas (55/57) and in 47.1% of the cases (8/17) of nodular goiter. Rb protein overexpression (more than 50% of positively staining cells) was found in 83.3% (10/12) of the follicular carcinomas, in 68.4% (39/57) of the follicular adenomas and in 11.8% (2/17) of the nodular goiters. The number of cases with Rb protein overexpression in the follicular carcinoma group did not differ significantly from that in the follicular adenoma group (p = 0.486). A positive correlation was found in the groups studied between the expressions of Rb protein and cyclin D1. However, the correlation was statistically significant only in the nodular goiter group (Rs = 0.567; p = 0.018). In the follicular carcinoma group, that correlation was borderline (Rp = 0.437; p = 0.072) and, in the follicular adenoma group, it was statistically insignificant (Rs = 0.217; p = 0.105). Our results confirm the existence of mutual regulation mechanisms of Rb and cyclin D1 protein expressions, which are observed in cells from various carcinomas.