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Biomedical subjects

L Plank

Publications and source records attributed to L Plank.

At least 19 recordsLinked to original sources

HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia.

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.

Adult↗

Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters.

The aim of this work was to determine the expression of the multidrug resistance (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related protein) and LRP (lung resistance-related protein), in 87 samples of breast carcinoma. Detection of these proteins was provided by using indirect enzymatic immunohistochemistry. Our findings were compared with the other clinical and pathological parameters: expression of Her2/neu, estrogen receptor status (ER), progesteron receptor status (PR), histological grade and regional lymph node status. For statistical analysis, non-parametric two sided Mann-Whitney-U test was used. Majority of breast carcinoma specimens show positivity for these proteins. The MDR1 and MRP1 signal was found in the cytoplasm of cancer cells. The expression of LRP was detected in the cytoplasm close to the nuclear membrane. The samples were positive for MDR1 protein in 57%, for MRP1 in 84% and for LRP in 79%. Comparing our results with other clinical and pathological parameters, negative correlation between ER, PR and MDR1 expressions and histological grading status was found. No associations were observed between the MRP1 and LRP proteins and histological grading, as well as between the expression of three MDR proteins and the other clinically relevant parameters. In conclusion, high frequency of expression of MDR proteins in breast carcinoma cells suggests, that these proteins might be an important factor of drug resistance in breast carcinoma. Nevertheless, the negative correlation between the histological grade of malignancy of tumor and the expression of ER, PR and MDR1 indicates possible influence of progressive tumor cell de-differentiation. However, this finding has to be confirmed in additional evaluations.

Biomarkers, Tumor↗

The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy.

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals just 1 hour after the end of oxygen exposure. Our results showed a tendency to a decrease in citric acid-induced cough in hyperoxic animals and an increase in animals with antioxidant therapy after hyperoxia. Antioxidant therapy significantly unblocked hyperoxia-induced down-regulation of cough (P=0.004). Significant changes also were obtained from mechanically-induced TBr cough [2.5(1-4) vs. 1.0(1-2); P<0.01] between the experimental and hyperoxic (control) animals. In conclusion, our results indicate a protective effect of antioxidant supplementation on oxidant-mediated cough depression.

Animals↗

Effects of thorax irradiation on citric acid-induced cough in guinea pigs.

Thoracic irradiation may cause an acute lymphocytic alveolitis or hypersensitivity pneumonitis. It is well known that cough reflex is sensitized by a number of inflammatory mediators. The purpose of the present study was to investigate the effect of the thoracic irradiation on the cough response in awake guinea pigs. Guinea pigs (Trik strain) were exposed to sham irradiation (n=16), a single irradiation dose of 10 Gy (n=12), and a fractionated irradiation dose (in five fractions) of 15 Gy (n=12) delivered to the thorax. Cough was induced by citric acid aerosol inhalation in gradually increasing concentrations (0.05-1.6 M) during the first week after thoracic irradiation. The cough response was expressed as a total number of coughs induced during all citric acid challenges. Irradiated animals with single dose of 10 Gy exhibited a time- dependent significant increase of citric acid-induced cough in the 6th day after irradiation compared with control animals (P=0.005), whereas cough was not altered significantly in irradiated animals with fractionated dose of 15 Gy. This study demonstrates that the increased cough response may be a determinant of the functional changes of airway nerve-endings mediating cough in the early phase after thoracic irradiation.

Animals↗

Early and late allergic phase related cough response in sensitized guinea pigs with experimental allergic rhinitis.

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

Allergens↗

The effect of chemical stimulation of esophageal mucosa on citric acid induced cough and specific airway resistance in guinea pig.

BACKGROUND: Gastroesophageal reflux disease is one of the most common causes of chronic cough. The mechanism of the cough initiation in these patients remains unresolved. OBJECTIVES: This study was designed to investigate the effect of intraesophageal (IE) administration of capsaicin on cough and specific airway resistance (Saw) in guinea pigs. METHODS: Male TRIK strain guinea pigs were used. In the first experiment 12 controls received IE saline, 9 animals (group 1) received IE capsaicin (400 microM, 0.2 ml) and 12 guinea pigs (group 2) received IE capsaicin (400 microM, 0.2 ml) 24 hours after IE administration of hydrochloric acid (3 M, 0.2 ml). Cough induced by inhalation of citric acid (CA) and Saw was determined after IE administration of saline in controls and capsaicin in groups 1 a 2. In the second experiment, CA induced cough was determined in guinea pigs (n=13) in the beginning of the study (control response), after NaOH (1 M, 0.2 ml) was administered IE. One week later in conditions of corrosive esophagitis CA induced cough was determined after IE administration of capsaicin (cough during esophageal stimulation). RESULTS: There was no difference in CA induced cough between controls, group 1 and 2 (p=0.98). Saw was hot affected by IE capsaicin stimulation and CA inhalation in group 1 and group 2. There was no difference found between control cough response and those induced after IE capsaicin in animals with corrosive esophagitis (p=0.75). CONCLUSION: Esophageal stimulation with capsaicin did not trigger and/or modulate CA induced cough and Saw in guinea pigs models. (Fig. 5, Ref. 22.)

Airway Resistance↗

Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs.

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol inhalation in gradually increasing concentration (0.05-1.6 M) and was evaluated before sensitization and then after the 1(st), 6(th), and 8(th) nasal challenge when rhinitis symptoms were most conspicuous. The intensity of cough was significantly increased after the first and repeated nasal OVA challenges, and reduced after the 8(th) NCh that was preceded with montelukast treatment [9(6-14) vs. 16.5(14-22) vs. 25.5(23-42) vs. 8.5(8-13); P=0.0003]. We conclude that antileukotriene therapy suppresses the stimulating effect of experimental allergic rhinitis on the chemically-induced cough in awake guinea pigs.

Acetates↗

[A congenital pulmonary arteriovenous fistula--a case report].

Congenital arteriovenous malformations are rare vascular anomalies in infancy and childhood. In most cases, these lesions consist of dilated vessels that appear as a large plexiform mass of vascular channels with direct communication between the pulmonary arteries and the pulmonary veins. Authors of the article present a case report of a newborn with a congenital arteriovenous fistula in the lower lobe of the right lung. They demonstrate various types, etiology, macroscopic and microscopic findings in this anomaly.

Arteriovenous Fistula↗

Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry.

AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.

Adult↗

[Maffucci's syndrome--case report of a 5-year-old female patient].

Maffucci's syndrome is a congenital non-hereditary syndrome characterized by a combination of dyschondroplasia (enchondromatosis) and haemangiomatosis. It is a rare disease. During the last 140 years only 200 cases were described [5]. 109 cases are described in the literature by other authors [21]. This disease is associated with a high risk of development of neoplastic processes, in particular sarcomatous transformation of enchondromatoses as well as other mesodermal and non-mesodermal malignities [13]. Based on the incidence of spinocellular haemangioendothelioma with other congenital syndromes, the presence at a young age of patients and the multicentric incidence support the assumption that spinocellular haemangioendothelioma may be the manifestation of genetically based mesodermal disease which may be associated with the picture of Maffucci's syndrome [6]. In their case-history the authors present a 5-year-old patient. They describe the clinical course and findings taking into account possible manifestations and risks associated with the disease. With regard to the low incidence of the disease and its interdisciplinary character the authors pen the question of possible causal, symptomatic or palliative treatment.

Child, Preschool↗

[Richter's syndrome (bimorphologic malignant lymphoma)].

Two distinct morphological types of malignant lymphoma in the same patient occur mostly due to transformation of a low grade lymphoma (CLL) into a large--cell non-Hodgkin lymphoma (high-grade lymphoma). Later reports have brough evidence of a clonal relationship between CLL and supervening NHL. The Richter's syndrome was found to be more frequent in patients with CLL displaying either multiple chromosomal aberrations or monoclonal gammapaties. In the last two decades reports have evidenced the existence of two types of the Richter's syndrome: one, the "classical" as a terminal event in a long evolving CLL, the other "variant" as the first clinical manifestation of a previously unrecognized subclinical CLL. Aggressive chemotherapy of CLL play a role in transformation of CLL to Richter's syndrome.

Cell Transformation, Neoplastic↗

[Primary mediastinal (thymus) large B-cell lymphoma: clinically defined type of tumors and morphologic variants].

In the WHO lymphoma classification, primary mediastinal (thymic) large B-cell lymphoma (PMVBL) is defined as a subtype of diffuse large B-cell lymphoma (DLBCL) showing typical clinical manifestation. The patterns related to variability of tumor cell morphology were analyzed in the setting of 15 bioptically verified PMVBL cases. In the majority of the cases (n = 12), the tumor showed pleomorphic blastic morphology with individual cell patterns resembling those of polymorphic centroblastoma of the Kiel classification. In addition, some of the cases had clear-cell and/or lacunar appearance (5/12), while distinctive anaplastic appearance was rare (1/12). Other cases (n = 3) showed a monotonous morphology of uniform smaller-sized blasts with monocytoid-like cytoplasm. The described morphologic variants of PMVBL might be related to the known genotypic variability of DLBCL, although monotypic c-Ig expression verified in some of the cases would support post-follicular stage of the tumor cell development. In the absence of clinical data and within the described morphologic variability, it is recommended to prefer a diagnosis of DLBCL and to include the tumor into a clinically defined subtype of PMVBL only in cases with well defined and typical clinical presentation and progression of the disease.

Adolescent↗

[Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization].

Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.

Adult↗

Salivary duct carcinoma--a highly aggressive salivary gland tumor with HER-2/neu oncoprotein overexpression.

Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.

Adult↗

Extraskeletal Ewing's sarcoma of the nose.

A 20-year-old woman presented with nasal obstruction and slight epistaxis. The obstructing lesion was excised and microscopy showed a neoplasm composed of comparatively uniform undifferentiated cells forming solid nests. The cytoplasm of the cells was clear but poorly demarcated, partly vacuolated and contained much glycogen. Although widespread in the nasal mucosa, the cells did not penetrate into the underlying bone. The cells expressed the MIC2 gene (using the CD99 marker). Electron microscopy showed simple cells with a small number of mitochondria, many glycogen particles; there were no neurosecretory granules present. Early surgical treatment followed by chemo- and radiotherapy have greatly improved the prognosis of EWS: extraskeletal Ewing's sarcoma (EWS/PNET).

12E7 Antigen↗

Frequency of eating occasions reported by young New Zealand Polynesian and European women.

The frequency of eating occasions reported by young New Zealand Polynesian and European women was examined. The timing and content of meals and snacks were analysed from 80 self-reported seven-day food diaries from a previous study of 80 young women (39 New Zealand Polynesian and 41 European) aged between 18 and 27 years. Nineteen Polynesian and 20 European women had a body mass index (BMI) greater than 30 kg.m-2 and were classified as obese. Breakfast was eaten more often by the European women than the Polynesian (median 4 versus 3 times.week-1, P = 0.012). Eleven (28%) of the Polynesian women skipped breakfast every day of the study week compared to only three (7%) of the Europeans (P = 0.019). Dinner was eaten more frequently by the European women (P = 0.020) who also ate significantly more meals during the week than the Polynesian (P = 0.039). Non-obese Europeans ate breakfast more frequently than their obese counterparts (P = 0.002) while no significant difference was observed between non-obese and obese Polynesians. The obese European and Polynesian groups reported similar patterns of breakfast consumption which differed significantly from the non-obese Europeans (P = 0.008). The young women in this study did not eat breakfast every day with the young Polynesian women eating fewer meals than the Europeans. There was an association between ethnic origin, body size and eating patterns in the women. These findings in comparison with previous studies in other countries indicate that the frequency of eating breakfast may be declining with time.

Adolescent↗

[Autoimmune hemolytic anemia and chronic giant cell hepatitis].

The authors describe a case report of a six months old boy with autoimmune hemolytic anemia and giant cell hepatitis. This is a very rare syndrome in infancy. After eleven months of intensive immunosuppressive treatment (glucocorticoids, cyclosporin A, azathioprin, intravenous immunoglobulins, cyclophosphamid) no improvement of hemolysis was observed and therefore splenectomy was indicated. 1 year after the treatment was finished the patient is in good general condition and his hematologic and biochemical parameters are physiological.

Anemia, Hemolytic, Autoimmune↗