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Biomedical subjects

J Dusková

Publications and source records attributed to J Dusková.

At least 19 recordsLinked to original sources

Association of PAX5 expression with clinical outcome in patients with TaT1 transitional cell carcinoma of the bladder.

OBJECTIVES: To assess the frequency and intensity of PAX5 gene messenger ribonucleic acid (mRNA) expression in TaT1 bladder cancer tissue, as well as its correlation with clinicopathologic variables and patient outcome. METHODS: The RNA expression of PAX5 was evaluated with reverse transcriptase polymerase chain reaction in the tumor tissue of 75 patients with stage TaT1 bladder cancer treated with transurethral resection. Patients were observed with cystoscopy and urinary cytologic evaluation. The association between PAX5 expression and clinicopathologic variables and patient outcome was evaluated. Benign urothelium from 8 patients with benign prostatic hyperplasia was obtained. These patients were used as a control group. RESULTS: PAX5 expression was found in 62 patients with bladder cancer (82.7%) but in no patient from the control group. High PAX5 expression (greater than 0.2) was confirmed in 19 patients (25.3%). No significant relationship was observed between quantity of PAX5 expression and clinicopathologic variables. The 3-year recurrence-free and progression-free survival rates in highly positive patients were 13.2% and 71.6%, compared with 40.6% and 92.8%, respectively, in patients with weak or negative expression (log-rank test, P = 0.0075, P = 0.022). Multivariate Cox proportional hazard model analysis identified PAX5 expression as an independent predictor of tumor recurrence. CONCLUSIONS: PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. High levels of PAX5 are associated with poorer recurrence-free and progression-free survival rates. Moreover, PAX5 expression was found to be an independent prognostic factor for recurrence-free survival by a multivariate analysis.

Adult↗

New multiple somatic mutations in the RET proto-oncogene associated with a sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs mostly as a sporadic tumor or in connection with inherited cancer syndromes-multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in the RET proto-oncogene are found in most of the familial cases. Somatic mutations in the RET proto-oncogene are detected in 23%-69% of patients with sporadic MTC. The most frequent somatic mutation is Met918Thr in exon 16 and only a small percentage of mutations in other RET exons have been observed. In a very few cases double mutations were found. Genetic screening for somatic mutations in RET exons 10, 11, 13, 14, 15, and 16 in Czech patients with sporadic MTC was carried out by DNA sequencing. This study presents a new triplesomatic mutation Gly911Asp, Met918Thr, and Glu921Lys in exon 16 of the RET proto-oncogene detected in an 18-year-old Czech male patient. In the second case, a new double-somatic mutation Val591Ile in exon 10 with a concomitant somatic mutation Met918Thr in exon 16 was found in a 77-year-old Czech female patient. These both newly described somatic multiple mutations were revealed in a hemizygous status, the loss of heterozygosity in tumor tissues in comparison with germline DNA was confirmed.

Adolescent↗

[Cervical cancer precursors: cytohistologic correlation with the results of HPV testing].

Persistence of high-risk types of human papillomavirus (HPV) is responsible for the development, maintenance and progression of squamous intraepithelial lesions (SILs). Cytohistologic correlation with the results of the HPV testing in 52 patients over a 3year period is presented. Two patients out of the 52 patients presented in this histologic follow up bore the diagnosis high-grade squamous intraepithelial lesion (HSIL) with the former cytology ASC-H. Low grade squamous intraepithelial lesions (LSIL) were found in eight patients, half of them diagnosed identically on cytology. Another four cases were formerly diagnosed cytologically as ASC-US. All women with the histologically confirmed dysplastic changes were HR HPV DNA positive. Our results indicate that significant histologic lesions may be discovered in patients exhibiting the high-risk HPV DNA positivity in the category of ASC-US (Atypical Squamous Cells of Undetermined Significance) and especially ASC-H (ASC cannot exclude high-grade squamous intraepithelial lesion). A combined screening test thus offers the possibility of greater protection and /or longer screening intervals.

Adult↗

Known pitfalls of the thyroid neoplasm diagnostics in the view of the new (2004) WHO Classification.

The new (2004) WHO Classification of Tumours of the Thyroid and Parathyroid Gland exhibits both formal and contentual changes compared to the previous one from the year 1988. Comparing both texts we have tried to apply the new norm to some recent diagnostic tasks. The classification of poorly differentiated and undifferentiated neoplasms has been successfully solved by employing the immunohistochemical procedures into the daily routine. Nevertheless, some diagnostic problems persist and can not be solved this way. This is true especially for the borderline neoplasm in the FVPTC category and even more for its oncocytic variant. There appeared shift in the criteria for the diagnosis of oncocytic variant of papillary carcinoma. Newly, the obligatory presence of the nuclei with the characteristics of the conventional papillary neoplasms is required. Thorough elaboration of the TNM system has solved the problem of multifocal lesion staging. Moreover, a web consultation source is recommended. The new Classification includes descriptions of the basic cytodiagnostic features. The post aspiration capsular damage consideration in relation to the diagnosis of the minimally invasive follicular carcinoma is one practical profit thereof. In terms of formal logic a criticisable feature of the new classification is the introduction of the so called "Synonyms". These listings include in fact partly real synonyms by definition, but together in one table quite often also subunits or variants of the nosologic units described. In general, the new Classification represents a successful consensus reached. As there are newly also references with varying opinions included, it is presented more like a point of gravity in this field than an undoubted truth. This also makes it a valuable and useful normative text.

Humans↗

[Paraneoplastic encephalitis].

Paraneoplastic neurodegenerative diseases are defined as damage to central and peripheral nervous tissue related to a malignancy, in the absence of metastases. If they represent first disease manifestation, the diagnosis can pose a real problem. A case of 59-year-old woman is described, who suffered during her last nine months of life from meningoencephalitis, with cranial nerves pareses and progressive quadruparalysis. The CSF exhibited a temporary inflammatory response with slow improvement, whereas the clinical status progressed continually toward terminal bronchopneumonia. An extensive infectious agent search was negative. Though the result of the autoantibody panel available (anti Yo, Hu, Ri) was negative, the paraneoplastic degeneration remained a part of the differential diagnosis. Post-mortem examination revealed residual brain stem meningoencephalitis and advanced cerebellar loss of Purkinje cells, in the presence of a neuroendocrine small cell lung carcinoma in the right lower lobe. The carcinoma only manifested intravitally, with paratracheal lymphadenomegaly on imaging. Rapid progress in the diagnostics of autoimmune neurodegeneration with the increasing spectrum of autoantibody detection tools has recently increased the possibilities of revealing clinically silent, primary manifesting neurodegeneration. In the future, it may also represent a target for therapeutic intervention.

Carcinoma, Small Cell↗

The prospects of advanced molecular methods in the detection of periodontal pathogens: hybridization in situ.

The paper summarizes the present state in the diagnostics of periodontal pathogens. Both the main advantages and drawbacks of the classic cultivation methods and those of the new DNA techniques are discussed. From the emerging methods of molecular diagnostics, the method of in situ hybridization is presented in more details. Its principle, various modifications of performance and possibilities of use are explained, including examples of its application in the detection of periodontal pathogens.

Bacteria↗

[Arbutin, salicin: the possibilities of their biotechnological production].

The paper aimed to transform exogenous precursors with in vitro cultures of Datura meteloides, Coronilla varia, Leuzea carthamoides and Schisandra chinensis. These cultures were added the precursors of arbutin and salicin (phenylalanine, cinnamic, p-coumaric, p-anisoic, o-coumaric, salicylic acids, salicylaldehyde, helicin), not yet tested by the present authors. The culture of Schisandra chinensis was also added, besides the above-mentioned precursors, hydroquinone, because this culture had not been employed for biotransformation purposes yet. The precursors tested were used in a concentration of 100 mg x l(-1) and the period of their action was 6; 12; 24; 48, and 168 hours. Positive results (both TLC and HPLC) in arbutin production were obtained in the culture of Schisandra chinensis after an addition of hydroquinone. The largest amount of arbutin in callus cultures was measured after a week's cultivation with hydroquinone (5.08 %). In this experimental variant, arbutin was released also to the culture medium. Our results revealed salicylaldehyde to be the optimal precursor of salicin. It was transformed by the culture of Datura meteloides after 6; 24, and 168 hours and by the culture of Coronilla varia after 6 hours. In comparison with arbutin, its amount was smaller.

Arbutin↗

[Expression of PAX2 and PAX8 genes in conventional type of renal carcinoma and their role in the tumor prognosis].

BACKGROUND: Sporadic renal cell carcinoma is one of the most common kidney malignancies in adults (85%). According to the IARC (The International Agency of Research on Cancer) Czech Republic has the first world position in the incidence and mortality for RCC. The prognosis of RCC is very poor because of high mortality around 70 to 50% and unpredictable progression after tumor removal. More precise molecular prognostic markers are required. Genes PAX2 and PAX8 control cell division during embryonic development and plays crucial role in tumor development because of stimulation of cell proliferation and/or inhibition of apoptotic program. METHODS AND RESULTS: Our RCC sample collection contains 64 tumor samples and 10 "normal" renal samples extracted from the affected kidney. mRNA was isolated from all samples and converted into cDNA. Expression of PAX genes was analyzed by using relative quantification real-time PCR with TaqMan labelled probe and GAPDH gene as an endogenous control. CONCLUSIONS: Expression of PAX2 gene was found in 97% and expression of PAX8 gene was found in 89% of analyzed tumor samples. The expression of both target genes was found in all "normal" renal samples. The level of expression of both PAX genes was very variable with the range from hundred times lower to forty times higher in comparison with the expression of chosen endogenous control. There were found no correlations between the expression of target genes and clinical-histological markers. These results do not have prognostic value yet because of short duration of patient observation. Follow-up clinical data are essential for completion of this research.

Biomarkers, Tumor↗

[Leonurus cardiaca in vitro].

Segments of sterile germinating plants were used to derive the tissue culture. Tests of the optimal hormonal composition of the medium from the standpoint of the growth of cultures revealed that the highest growth in biomass was achieved in the medium with an addition of 2.4-D (0.1, 1.0 mg.l-1), NAA (10.0 mg.l-1), and a combination of IAA (1.0 mg.l-1) + K (1.0 mg.l-1). The difference between these values was statistically insignificant. Other tested concentrations of growth regulators showed statistically significantly lower increases. The effects of different types of growth regulators and their concentrations on the production of selected metabolites in the tissue cultures were also examined and compared with the results obtained from the extract of the drug. Of alkaloids, stachydrine was demonstrated both in the extract of the drug and the extracts from all tested calluses regardless of the type and concentration of the growth regulator. Of flavonoid substances, two stains were demonstrated in the extract from the drug as well as in the extracts from all tested calluses. Neither of them was identical with the employed standards of rutin and quercetin. The results of TLC of iridoid substances were different in the extract from the drug (12 stains) and in the extracts from calluses (4 stains--3 identical with the stains in the extract from the drug). As to saccharides, three of them--glucose, fructose, and sucrose--were identified in the extract of the drug as well as in the extracts from all calluses.

Culture Techniques↗

[A case of a patient with solitary prostate metastasis of the colorectal carcinoma three years after abdominoperineal amputation of the rectum].

AIM: The aim of this study is to present a case-review of a patient with an extremely rare finding of a solitary metastasis of the colorectal carcinoma in his prostate. METHODOLOGY: A Case-Review. RESULTS: The study describes a case of a 42-year-old patient who underwent abdominoperineal amputation for the rectal carcinoma pT3 N1 M0 with complementary actinotherapy and chemotherapy. Three years after his rectum amputation, a CT scan disclosed a hypodense focus in his prostate of unknown origin. Elevation of the CEA was found upon laboratory examination, other tumor markers including the PSA were not abnormal. The positron emission tomography (PET) did not disclose other distant foci. The patient was administered 4 courses of chemotherapy with, basically, no signs of regression in the prostate foci. Biopsy from the suspicious focus was conducted transperitoneally, followed by its histological examination which confirmed cribriform adenocarcinoma. Our team decided on salvage cystoprostatectomy, securing urine derivation by the ilium conduit. 6 months later, the CT examination showed a massive local relapse and two metastatic foci in the liver, further oncological therapy was not indicated. The patient died 7 moths after the radical cystoprostatectomy. CONCLUSION: This case-review points out a possibility of metastatic prostate affections connected to the colorectal carcinoma disorder, as well as its treatment procedures.

Adenocarcinoma↗

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

OBJECTIVES: The expression pattern of PAX5 in the tissue of superficial bladder transitional cell carcinoma (TCC), its prognostic value and its correlation with p53 immunohistochemistry and p53 mutation analysis were evaluated. METHODS: Study comprised 61 patients with histologically confirmed superficial bladder TCC. Expression level of PAX5 mRNA was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and determined semiquantitatively. The presence of p53 mutations was determined by SSCP and confirmed by direct sequencing. The p53 immunohistochemistry was performed with DO1 antibody and semiquantitatively evaluated using HSCORE (HS) method. As the control group for the evaluation of the PAX5 expression served 8 men with benign prostatic hyperplasia. RESULTS: PAX5 expression was found in 50 patients with bladder TCC but in no patient from the control group. Its quantity however correlated neither with the stage nor with the grade of the tumor. P53 mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5 (deletion of proline 128). On the contrary, positive immunohistochemical staining of p53 was detected in most patients. Using the cutoff value of HS 200, 56.9% of patients showed p53 overexpression. Quantity of p53 immunochistochemical positivity did not correlate with the quantity of PAX5 expression. Using the cutoff values of HS 200 for p53 and of 0.2 for PAX5, 7 of 8 patients with future progression had p53 and 4 had PAX5 overexpression respectively. CONCLUSION: The expression of gene PAX5 is a frequent event in superficial TCC of the bladder.

Aged↗

[Laparoscopic transperitoneal adrenalectomy in hormonally-active adrenal tumors].

Laparoscopic adrenalectomy is considered the "gold standard" in adrenal surgery for benign functioning (and non-functioning) tumors. Laparoscopy meets criteria of miniinvasive surgery with minimal postoperative pain, short hospital stay and an outstanding cosmetic effect, the radicality of the procedure, open surgery and laparoscopy are equally effective. In cooperation with endocrinological department focused on detection of functioning adrenal tumors, the diagnostic and therapeutic procedure seems to be very efficient, so that the primary goal of rapid cure could be achieved. Patients after laparoscopic adrenalectomy mostly do not need chronic antihypertensive medication and only those after bilateral adrenalectomy (Cushing's disease) require life-long low dose hydrocortisone therapy. In pheochromocytomas, total excision of the tumor is considered to be a life-saving procedure, although up to 20% may recur as hereditary or as a part of von Hippel-Lindau's disease.

Adrenal Cortex Hormones↗

[Meningeal carcinomatosis as the first manifestation of gastric adenocarcinoma].

Gastric adenocarcinoma is rarely observed in patients under the age of 40. Meningeal carcinomatosis as a first manifestation of disease is absolutely unique. If meningeal involvement occurs it is usually secondary event in previously diagnosed tumor. The prognosis is very unfavorable associated with short term survival. In the treatment of this disease there night be used either chemotherapy administered via lumbar injection or radiotherapy or combination of both. This case study is one of very few cases reported in literature when meningeal carcinomatosis was a first sign of advanced gastric adenocarcinoma. 39 years old woman was admitted to our hospital with severe headache, diplopia and vomiting. Meningeal carcinomatosis with gastric primary was diagnosed. She was treated with combination of cytosine arabinosid (Cytosar), methotrexate (Methotrexat), hydrocortisone (Hydrocortisone) administered via intrathecal lumbar injection and whole brain radiation. As a main complication she experienced disseminated intravascular coagulopathy. The improvement of patient's condition following the initial treatment had a very limited duration and the patient died of bilateral pneumonia and cerebral edema 44th day after the admission.

Adenocarcinoma↗

[Pulmonary endometriosis].

Endometriosis in less common locations can become a diagnostic pitfall both from the clinical and morphological point of view, as this diagnosis is only seldom considered in the first series of differential diagnoses. This was true also for our patient reported. 48-year-old woman underwent left superior lobectomy for the clinical diagnosis of pulmonary neoplasm. Slightly prominent subpleural whitish nodular partly cystic tissue was histologically identified as pulmonary endometriosis. It consisted of proliferative to hyperproliferative endometrial glands surrounded by proliferation type stroma. Focally slight cytological glandular atyplas and immature squamous metaplasia were present. Later another focus was located by x-ray examination. Without any surgery, it responded to six month treatment with competitive gonadoliberin agonist (GnRH analogue) Zoladex. Three years after the treatment no signs of the disease have been present. The correct clinical diagnosis accompanied with cautious morphological verification may prevent unnecessary extensive surgery. However, even some correctly diagnosed and morphologically verified cases may require radical operative removal. Either approach (conservative therapy and surgery) completed with subsequent dispensarisation may prevent both the common (cycle related progressive tissue damage) and rare (tissue destruction, malignant transformation) complications.

Diagnosis, Differential↗

A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1 protease.

Crystallization conditions for an HIV-1 protease-inhibitor complex were optimized to produce crystals suitable for X-ray diffraction experiments. The X-ray structure of the HIV-1 protease complex was solved and refined at 3.1 A resolution. In contrast to Saquinavir, the mimetic hydroxy group of the inhibitor Boc-Phe-Psi[(S)-CH(OH)CH(2)NH]-Phe-Glu-Phe-NH(2) is placed asymmetrically with respect to the non-crystallographic twofold axis of the protease dimer so that hydrogen bonds between the amino group of the inhibitor and the catalytic aspartates can be formed. The inhibitor binds in the centre of the active site by a compact network of hydrogen bonds to Gly27, Gly127, Asp25, Asp125 and via the buried water molecule W301 to Ile50 and Ile150.

Aspartic Acid↗

[Factors which affect cytodiagnosis in gynecology].

The incidence of invasive carcinoma of the cervix in the Czech Republic is higher than in Western Europe. The only effective test for early discovery of the precancerous lesions is cytodiagnostics--"PAP" smears. The study points to preventing mistakes in the cytodiagnostic process and stresses quality control according to the International Academy of Cytology (I.A.C.) and the European Federation of Cytological Societies (E.F.C.S.).

Adult↗

[Bergenia crassifolia (L.) Fritsch in vitro].

Sterile germinating plants were used to derive a tissue culture. The greatest stimulating effect on the growth of the culture was exerted by NAA cultures in all concentrations tested, by IAA in concentrations of 1.0 and 10.0 mg.l-1, by IBA in a concentration of 0.1 mg.l-1, and by the combination of IBA + K. The difference between the values of growth on these media was statistically insignificant. TLC analysis of callus extracts demonstrated the presence of bergenin, arbutin, hydroquinone, and methylarbutine. HPLC analysis confirmed the findings (arbutin 0.25%, hydroquinone 0.05%, methylarbutin 0.28%). The results of biotransformation tests show that the highest increase in arbutin took place after addition of 4-hydroxybenzoic acid and withdrawal of the sample after 24 hours (3.82%). No transformation of arbutin or 4-methoxyphenol to produce methylarbutin took place in the culture under the given conditions. The highest increase in the summary content of phenolic substances occurred with the use of the elicitor Pseudomonas aeruginosa--88% (conc. 0.0001 g/100 ml, 12-hour action).

Arbutin↗

[Multihormonal and multifunctional hypophyseal adenoma and the acromegaly syndrome].

Woman 75-year-old treated 30 years for syndrome of acromegaly refused pituitary surgery and irradiation. Five years and nine months before death she had a colon carcinoma successfully removed. Multinodular hyperfunctional goitre was treated with carbimazole. For six last years of life corticosteroids were given as a replacement therapy. Her cause of death was the heart failure due to acromegalic heart disease. In autopsy a large intrasellar and extrasellar pituitary adenoma without rests of nonneoplastic tissue was found. Nevertheless the target peripheral endocrine glands except ovaries, were not atrophic. A multinodular goitre and diffuse adrenocortical hyperplasia were revealed. Histology, and immunohistochemistry demonstrated that mot neoplastic cells were producing GH and ACTH, dispersly Prl, scattered cells were positive for beta-subunit of FSH, LH, TSH. Electron microscopy proved most of the cells to be densely granulated. We classify the adenoma according to the newly proposed WHO pituitary tumours classification (1) as plurihormonal, hyperfunctional, extrasellar, typical adenoma from densely granulated cells. We conclude that in plurihormonal adenomas with dominant (in the case referred acromegalic) symptomatology the additional hormonal production should be monitored as a possible source of important complications.

Acromegaly↗