A case report of a 70-year-old woman who had never suffered from any eye disease is presented. It was found that 2 weeks prior to the ophthalmological examination at another clinic 'something fell' into her right eye; she noticed a decline in the vision of her the left eye. On ophthalmologic examination Visual Acuity, Right Eye (VARE) was 0.4 and Visual Acuity, Left Eye (VALE): fingers at 1 m. Incipient cataracts in both eyes, more on the right. On optic nerve (ON) evaluation, the optic papilla cup-to-disk ratio (C/D) was=0.6 and 0.7, R/L, respectively. A total of 1 month after the first examination VARE was found: 0.4 and VALE: 0.16. The cataracts did not correspond to the decrease in visual acuity. an excavation on the right papilla (C/D=0.6) was found and the left papilla was atrophic (C/D=0.7). Otherwise, the fundus evaluation was normal. Incomplete upper temporal quadrantanopia on the right visual field (VF) and temporal hemianopia extending into the central part on the left VF were identified. An electrophysiological examination (pattern visual evoked responses) showed a marked decrease in amplitudes on the right and no prolongation of P100 latency; a non-excitable reaction was observed in the left. Our finding was chiasmatic syndrome with more significant impairment on the left side. Subsequent magnetic resonance imaging (MRI) was suspicious for Rathke's cleft cyst (RCC). A neurosurgical intervention was performed the week following MRI . Using a subfrontal approach via a small right frontal craniotomy, the tumor was released from surrounding neural structures and radically removed using microsurgical techniques. During the procedure, it was not completely clear whether it was RCC or a craniopharyngioma; the biopsy findings were consistent with RCC with xanthogranulomatous changes. The authors emphasize the importance of visual field examination in unclear visual disorders, as well as the importance of follow-up examinations to uncover recurrences.

• Klíčová slova
• Rathke cleft cysts, imaging methods, therapy, visual field,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Myoepithelial carcinoma of salivary glands is an underrecognized and challenging entity with a broad morphologic spectrum, including an EWSR1-rearranged clear cell variant. Myoepithelial carcinoma is generally aggressive with largely unknown genetic features. A retrospective review of Salivary Gland Tumor Registry in Pilsen searching for the key words "clear cell myoepithelial carcinoma," "hyalinizing clear cell," and "clear cell malignant myoepithelioma" yielded 94 clear cell myoepithelial carcinomas (CCMCs) for molecular analysis of EWSR1 rearrangement using fluorescence in situ hybridization (FISH). Tumors positive for EWSR1 gene rearrangement were tested by next-generation sequencing (NGS) using fusion-detecting panels. NGS results were confirmed by reverse-transcription polymerase chain reaction or by FISH. Twenty-six tumors originally diagnosed as CCMC (26/94, 27.6%) revealed split signals for EWSR1 by FISH. Six of these tumors (6/26, 23%) displayed amplification of the EWSR1 locus. Fifteen cases were analyzable by NGS, whereas 9 were not, and tissue was not available in 2 cases. None of the CCMCs with EWSR1 rearrangements detected by FISH had an EWSR1 fusion transcript. Fusion transcripts were detected in 6 cases (6/15, 40%), including LIFR-PLAG1 and CTNNB1-PLAG1, in 2 cases each, and CHCHD7-PLAG1 and EWSR1-ATF1 fusions were identified in 1 case each. Seven cases, including those with PLAG1 fusion, were positive for PLAG1 rearrangement by FISH, with notable exception of CHCHD7-PLAG1, which is an inversion not detectable by FISH. One single case with EWSR1-ATF1 fusion in NGS showed ATF1 gene rearrangement by FISH and was reclassified as clear cell carcinoma (CCC). In addition, another 4 cases revealed ATF1 rearrangement by FISH and were reclassified as CCC as well. Moreover, 12/68 (17%) CCMCs with intact EWSR1 gene were selected randomly and analyzed by NGS. PLAG1 fusions were found in 5 cases (5/12, 41.6%) with LIFR (2 cases), FGFR1 (2 cases), and CTNNB1 (1 case) as partner genes. Overall, PLAG1 gene rearrangements were detected in 10/38 (26%) tested cases. None of the tumors had SMARCB1 loss by immunohistochemistry as a possible explanation for the EWSR1 abnormalities in FISH. Novel findings in our NGS study suggest that EWSR1-FISH positive CCMC is a gene fusion-driven disease with frequent oncogenic PLAG1 fusions, including LIFR-PLAG1 and CTNNB1-PLAG1 in most cases. Productive EWSR1 fusions are found only in a minority of EWSR1-ATF1-rearranged cases, which were in part reclassifiable as CCCs. Detectable EWSR1-FISH abnormality in CCMCs without gene fusion perhaps represents a passenger mutation with minor or no oncologic effect.

• MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• genová přestavba MeSH
• lidé středního věku MeSH
• lidé MeSH
• myoepiteliální nádor genetika   MeSH
• nádory slinných žláz genetika   MeSH
• onkogenní fúze MeSH
• protein EWS vázající RNA genetika   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• EWSR1 protein, human MeSH Prohlížeč
• PLAG1 protein, human MeSH Prohlížeč
• protein EWS vázající RNA MeSH

The emergence of cisplatin (CDDP) resistance is the main cause of treatment failure and death in patients with testicular germ cell tumors (TGCT), but its biologic background is poorly understood. To study the molecular basis of CDDP resistance in TGCT we prepared and sequenced CDDP-exposed TGCT cell lines as well as 31 primary patients' samples. Long-term exposure to CDDP increased the CDDP resistance 10 times in the NCCIT cell line, while no major resistance was achieved in Tera-2. Development of CDDP resistance was accompanied by changes in the cell cycle (increase in G1 and decrease in S-fraction), increased number of acquired mutations, of which 3 were present within ATRX gene, as well as changes in gene expression pattern. Copy number variation analysis showed, apart from obligatory gain of 12p, several other large-scale gains (chr 1, 17, 20, 21) and losses (chr X), with additional more CNVs found in CDDP-resistant cells (e.g., further losses on chr 1, 4, 18, and gain on chr 8). In the patients' samples, those who developed CDDP resistance and died of TGCT (2/31) showed high numbers of acquired aberrations, both SNPs and CNVs, and harbored mutations in genes potentially relevant to TGCT development (e.g., TRERF1, TFAP2C in one patient, MAP2K1 and NSD1 in another one). Among all primary tumor samples, the most commonly mutated gene was NSD1, affected in 9/31 patients. This gene encoding histone methyl transferase was also downregulated and identified among the 50 most differentially expressed genes in CDDP-resistant NCCIT cell line. Interestingly, 2/31 TGCT patients harbored mutations in the ATRX gene encoding a chromatin modifier that has been shown to have a critical function in sexual differentiation. Our research newly highlights its probable involvement also in testicular tumors. Both findings support the emerging role of altered epigenetic gene regulation in TGCT and CDDP resistance development.

• Klíčová slova
• cell cycle, cisplatin resistance, molecular aberrations, next generation sequencing, testicular germ cell tumor,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Panniculitis-like T-cell lymphoma is an uncommon type of non-Hodgkin lymphoma, occurring usually in the form of nodules within the subcutaneous fat tissue of the extremities or trunk. In the literature, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is described as a distinct type of T-cell lymphoma with a variable clinical behavior, depending on molecular phenotype of T-cell receptor (TCR) and on the presence or absence of hemophagocytic syndrome. CASE PRESENTATION: We present a bioptic and autoptic case of a 65-years old Caucasian man with panniculitic T-cell lymphoma with morphological and immunohistochemical features of SPTCL, limited to the retroperitoneal and mesenteric mass, i.e. without any cutaneous involvement, and associated with severe hemophagocytic lymphohistiocytosis. CONCLUSION: A panniculitic T-cell lymphoma with morphological and molecular features of SPTCL, which is limited to mesentery, i.e. does not involve subcutaneous fat, seems to be exceedingly rare.

• Klíčová slova
• Hemophagocytosis, Lymphohistiocytosis, Mesentery, Panniculitis, T-cell lymphoma,
• MeSH
• diferenciální diagnóza MeSH
• kožní T-buněčný lymfom diagnóza   patologie   MeSH
• lidé MeSH
• lymfohistiocytóza hemofagocytární diagnóza   patologie   MeSH
• lymfom T-buněčný diagnóza   patologie   MeSH
• nádory kůže diagnóza   patologie   MeSH
• panniculitis diagnóza   patologie   MeSH
• pitva MeSH
• senioři MeSH
• T-lymfocyty patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

OBJECTIVE: AIDS-related mortality has changed dramatically with the onset of highly active antiretroviral therapy (HAART), which has even allowed compensated HIV-infected patients to withdraw from secondary therapy directed against opportunistic pathogens. However, in recently autopsied HIV-infected patients, we observed that associations with a broad spectrum of pathogens remain, although detailed analyses are lacking. Therefore, we focused on the possible frequency and spectrum shifts in pathogens associated with autopsied HIV-infected patients. DESIGN: We hypothesized that the pathogens frequency and spectrum changes found in HIV-infected patients examined postmortem did not recapitulate the changes found previously in HIV-infected patients examined antemortem in both the pre- and post-HAART eras. Because this is the first comprehensive study originating from Central and Eastern Europe, we also compared our data with those obtained in the West and Southwest Europe, USA and Latin America. METHODS: We performed autopsies on 124 HIV-infected patients who died from AIDS or other co-morbidities in the Czech Republic between 1985 and 2014. The pathological findings were retrieved from the full postmortem examinations and autopsy records. RESULTS: We collected a total of 502 host-pathogen records covering 82 pathogen species, a spectrum that did not change according to patients' therapy or since the onset of the epidemics, which can probably be explained by the fact that even recently deceased patients were usually decompensated (in 95% of the cases, the last available CD4+ cell count was falling below 200 cells*μl-1) regardless of the treatment they received. The newly identified pathogen taxa in HIV-infected patients included Acinetobacter calcoaceticus, Aerococcus viridans and Escherichia hermannii. We observed a very limited overlap in both the spectra and frequencies of the pathogen species found postmortem in HIV-infected patients in Europe, the USA and Latin America. CONCLUSIONS: The shifts documented previously in compensated HIV-infected patients examined antemortem in the post-HAART era are not recapitulated in mostly decompensated HIV-infected patients examined postmortem.

• MeSH
• charakteristiky bydlení MeSH
• dospělí MeSH
• druhová specificita MeSH
• HIV infekce farmakoterapie   imunologie   MeSH
• lidé MeSH
• oportunní infekce doprovázející AIDS imunologie   MeSH
• pitva MeSH
• počet CD4 lymfocytů MeSH
• posmrtné změny * MeSH
• vysoce aktivní antiretrovirová terapie * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk. METHODS: A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. RESULTS: PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305). CONCLUSIONS: Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.

• MeSH
• Alphapapillomavirus imunologie   MeSH
• Chlamydia trachomatis imunologie   MeSH
• Cytomegalovirus imunologie   MeSH
• dospělí MeSH
• druhová specificita MeSH
• ELISA MeSH
• fluorescenční protilátková technika nepřímá MeSH
• hyperplazie prostaty krev   imunologie   MeSH
• komplement fixační testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské urogenitální nemoci imunologie   mikrobiologie   virologie   MeSH
• Mycoplasma hominis imunologie   MeSH
• nádory prostaty krev   imunologie   MeSH
• Neisseria gonorrhoeae imunologie   MeSH
• prostata patologie   chirurgie   MeSH
• prostatektomie MeSH
• protilátky bakteriální krev   MeSH
• protilátky virové krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Simplexvirus imunologie   MeSH
• studie případů a kontrol MeSH
• Treponema pallidum imunologie   MeSH
• Ureaplasma urealyticum imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protilátky bakteriální MeSH
• protilátky virové MeSH

Approximately 15% of men with newly diagnosed cancer are younger than 55 years, and about 26% of them are younger than 20 years. However the most common cause of fertility disorders is oncological treatment itself, the oncological diseases, changes in anatomy, and primary or secondary hormonal insufficiency are also significant factors. The chemotherapy, radiation, or their combination reduce sperm count, impair sperm motility and cause disorders in morphology and DNA integrity. Prognosis of sperm production recovery depends on the type of cancer, stage of the disease, patient age, drug treatment, treatment route and dosage, and pre-treatment male fertility.

• MeSH
• lidé MeSH
• mužská infertilita etiologie   MeSH
• nádory terapie   MeSH
• protinádorové látky škodlivé účinky   MeSH
• radioterapie škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky MeSH

As life expectancy of patients infected by Human Immunodeficiency Virus (HIV) has prolonged, they are treated by physicians of different specialities. This article focuses on urologic complications of HIV infection. Urinary tract infections in HIV positive patients are more frequent than in otherwise healthy individuals and less common microorganisms can be involved. Sexually transmitted diseases are a commonplace. Certain malignancies of the genitourinary tract are more often diagnosed in HIV positive than in HIV negative population. Impairment of kidney function is usually caused by HIV-associated nephropathy. Acute renal failure can also occur. Indinavir causes urinary stones formation. Male circumcision is an effective method of HIV transmission prevention.

• MeSH
• HIV infekce komplikace   prevence a kontrola   MeSH
• infekce močového ústrojí komplikace   MeSH
• lidé MeSH
• nefropatie doprovázející AIDS komplikace   MeSH
• urogenitální nádory komplikace   MeSH
• urologické nemoci komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertension (late-onset treatment). TGR and control Hannover Sprague-Dawley (HanSD) rats were fed a high-salt diet and were treated concomitantly with the nonselective ET(A/B) receptor blocker bosentan or the selective ET(A) receptor blocker atrasentan from day 52 of age on. Survival rate was partly increased by bosentan and fully normalized with atrasentan. Bosentan transiently decreased blood pressure (BP), whereas atrasentan significantly reduced BP as early as one week after the start of the treatment. This effect persisted for the whole experimental period. Atrasentan also substantially reduced cardiac hypertrophy, proteinuria, glomerulosclerosis and left ventricle ET-1 content. Bosentan improved and atrasentan almost restored podocyte architecture and reversed changes in podocyte phenotype represented by the expression of CD 10, desmin and vimentin. Our results demonstrate that selective ET(A) receptor blockade has more favorable effects than nonselective ET(A/B) receptor blockade and, unlike observed in homozygous TGR, ET(A) receptor blockade has similar effects in heterozygous rats with established hypertension as in young animals with developing hypertension.

• MeSH
• angiotensin II fyziologie   MeSH
• antagonisté endotelinového receptoru * MeSH
• elektronová mikroskopie MeSH
• endotelin-1 metabolismus   MeSH
• fokálně segmentální glomeruloskleróza patologie   MeSH
• geneticky modifikovaná zvířata MeSH
• heterozygot MeSH
• hypertenze maligní farmakoterapie   genetika   patologie   MeSH
• imunohistochemie MeSH
• krevní tlak účinky léků   genetika   MeSH
• krysa rodu Rattus MeSH
• ledviny patologie   MeSH
• míra přežití MeSH
• potkani Sprague-Dawley MeSH
• proteinurie genetika   MeSH
• renin genetika   fyziologie   MeSH
• sodík dietní farmakologie   MeSH
• tělesná hmotnost genetika   MeSH
• velikost orgánu genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• angiotensin II MeSH
• antagonisté endotelinového receptoru * MeSH
• endotelin-1 MeSH
• renin MeSH
• sodík dietní MeSH

The aim of the present study was to evaluate the effects of inhibition of cytochrome P-450 (CYP) activity by 1-aminobenzotriazole (ABT) and by CoCl(2), first, on the development of hypertension when treatment was started in young male heterozygous Ren-2 transgenic rats (TGR) and, second, on blood pressure (BP) when treatment was started in adult TGR with established hypertension. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. In addition, the renal cortical activities of omega-hydroxylase, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of epoxygenase, the enzyme responsible for epoxyeicosatrienoic acids (EETs) production, and urinary excretion of 20-HETE and EETs in TGR and HanSD rats were assessed. TGR have higher renal tissue omega-hydroxylase activity and urinary excretion of 20-HETE but have significantly lower renal epoxygenase activity and urinary excretion of EETs than HanSD rats. Treatment of young TGR with ABT and CoCl(2) attenuated the development of hypertension and cardiac hypertrophy and prevented glomerulosclerosis. Administration of ABT and CoCl(2) in adult TGR decreased BP, cardiac hypertrophy, but did not reduce glomerulosclerosis. Our data suggest that altered production and/or action of CYP-derived metabolites play a permissive role in the development and maintenance of hypertension in TGR by enhancing ANG II-induced vasoconstriction.

• MeSH
• cytochrom P-450 CYP2J2 MeSH
• cytochrom P450 CYP4A metabolismus   MeSH
• fokálně segmentální glomeruloskleróza patofyziologie   MeSH
• heterozygot MeSH
• hypertenze patofyziologie   MeSH
• inhibitory cytochromu P450 * MeSH
• inhibitory enzymů farmakologie   MeSH
• kardiomegalie patofyziologie   MeSH
• kobalt MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• kůra ledviny MeSH
• kyseliny hydroxyeikosatetraenové biosyntéza   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• oxygenasy metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• renin-angiotensin systém fyziologie   MeSH
• renin genetika   metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• triazoly farmakologie   MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 1-aminobenzotriazole MeSH Prohlížeč
• 20-hydroxy-5,8,11,14-eicosatetraenoic acid MeSH Prohlížeč
• cobaltous chloride MeSH Prohlížeč
• cytochrom P-450 CYP2J2 MeSH
• cytochrom P450 CYP4A MeSH
• inhibitory cytochromu P450 * MeSH
• inhibitory enzymů MeSH
• kobalt MeSH
• kyseliny hydroxyeikosatetraenové MeSH
• oxygenasy MeSH
• renin MeSH
• systém (enzymů) cytochromů P-450 MeSH
• triazoly MeSH