Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.

• MeSH
• adenoidně cystický karcinom mortalita   patologie   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny patologie   MeSH
• nádory slinných žláz mortalita   patologie   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD). OBJECTIVE: Contrast results from computer versus real-space versions of the HGT. METHODS: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. RESULTS: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. CONCLUSIONS: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

• MeSH
• Alzheimerova nemoc komplikace   diagnóza   MeSH
• bludiště - učení fyziologie   MeSH
• diagnóza počítačová metody   MeSH
• kognitivní poruchy komplikace   diagnóza   MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• progrese nemoci MeSH
• psychiatrické posuzovací škály MeSH
• regresní analýza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vnímání prostoru fyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of salivary gland neoplasms greatly influences macroscopic and microscopic evaluation of the specimen but also, given the high incidence of metastases and morbidity, carries significant treatment implications.

• MeSH
• dospělí MeSH
• geny myc genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorová transformace buněk patologie   MeSH
• nádory slinných žláz diagnóza   patologie   MeSH
• prognóza MeSH
• sekundární malignity diagnóza   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

• MeSH
• dediferenciace buněk fyziologie   MeSH
• karcinom genetika   patologie   MeSH
• lidé MeSH
• nádorová transformace buněk genetika   patologie   MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz genetika   patologie   MeSH
• receptor erbB-2 genetika   MeSH
• slinné žlázy patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Bacteria influence eukaryotic biology as parasitic, commensal or beneficial symbionts. Aside from these organismal interactions, bacteria have also been important sources of new genetic sequences through horizontal gene transfer (HGT) for eukaryotes. In this Review, we focus on gene transfers from bacteria to eukaryotes, discuss how horizontally transferred genes become functional and explore what functions are endowed upon a broad diversity of eukaryotes by genes derived from bacteria. We classify HGT events into two broad types: those that maintain pre-existing functions and those that provide the recipient with new functionality, including altered host nutrition, protection and adaptation to extreme environments.

• MeSH
• Bacteria genetika   MeSH
• biologická evoluce MeSH
• Eukaryota genetika   MeSH
• fyziologická adaptace genetika   MeSH
• přenos genů horizontální fyziologie   MeSH
• regulace genové exprese MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.

• MeSH
• antibakteriální látky MeSH
• Bacteria genetika   MeSH
• bakteriální geny MeSH
• genom bakteriální MeSH
• mikrobiota * MeSH
• prasata MeSH
• přenos genů horizontální * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Acquisition of genes by plastid genomes (plastomes) via horizontal gene transfer (HGT) seems to be a rare phenomenon. Here, we report an interesting case of HGT revealed by sequencing the plastomes of the eustigmatophyte algae Monodopsis sp. MarTras21 and Vischeria sp. CAUP Q 202. These plastomes proved to harbour a unique cluster of six genes, most probably acquired from a bacterium of the phylum Bacteroidetes, with homologues in various bacteria, typically organized in a conserved uncharacterized putative operon. Sequence analyses of the six proteins encoded by the operon yielded the following annotation for them: (i) a novel family without discernible homologues; (ii) a new family within the superfamily of metallo-dependent hydrolases; (iii) a novel subgroup of the UbiA superfamily of prenyl transferases; (iv) a new clade within the sugar phosphate cyclase superfamily; (v) a new family within the xylose isomerase-like superfamily; and (vi) a hydrolase for a phosphate moiety-containing substrate. We suggest that the operon encodes enzymes of a pathway synthesizing an isoprenoid-cyclitol-derived compound, possibly an antimicrobial or other protective substance. To the best of our knowledge, this is the first report of an expansion of the metabolic capacity of a plastid mediated by HGT into the plastid genome.

• MeSH
• anotace sekvence MeSH
• bakteriální geny MeSH
• DNA řas genetika   MeSH
• genom plastidový * MeSH
• Heterokontophyta genetika   MeSH
• molekulární evoluce MeSH
• multigenová rodina MeSH
• přenos genů horizontální * MeSH
• sekvenční analýza DNA metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.

• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• indany farmakologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• skopolamin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Few cases of spontaneously horizontally transferred bacterial genes into plant genomes have been described to date. The occurrence of horizontally transferred genes from the T-DNA of Agrobacterium rhizogenes into the plant genome has been reported in the genus Nicotiana and in the species Linaria vulgaris. Here we compare patterns of evolution in one of these genes (a gene encoding mikimopine synthase, mis) following three different events of horizontal gene transfer (HGT). As this gene plays an important role in Agrobacterium, and there are known cases showing that genes from pathogens can acquire plant protection function, we hypothesised that in at least some of the studied species we will find signs of selective pressures influencing mis sequence. The mikimopine synthase (mis) gene evolved in a different manner in the branch leading to Nicotiana tabacum and N. tomentosiformis, in the branch leading to N. glauca and in the genus Linaria. Our analyses of the genus Linaria suggest that the mis gene began to degenerate soon after the HGT. In contrast, in the case of N. glauca, the mis gene evolved under significant selective pressures. This suggests a possible role of mikimopine synthase in current N. glauca and its ancestor(s). In N. tabacum and N. tomentosiformis, the mis gene has a common frameshift mutation that disrupted its open reading frame. Interestingly, our results suggest that in spite of the frameshift, the mis gene could evolve under selective pressures. This sequence may still have some regulatory role at the RNA level as suggested by coverage of this sequence by small RNAs in N. tabacum.

• MeSH
• Agrobacterium enzymologie   genetika   MeSH
• bakteriální proteiny klasifikace   genetika   metabolismus   MeSH
• druhová specificita MeSH
• fylogeneze MeSH
• imidazoly metabolismus   MeSH
• interakce hostitele a patogenu genetika   MeSH
• Linaria genetika   mikrobiologie   MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• oxidoreduktasy působící na CH-NH vazby klasifikace   genetika   metabolismus   MeSH
• posunová mutace MeSH
• přenos genů horizontální * MeSH
• pyridiny metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• sekvence nukleotidů MeSH
• selekce (genetika) MeSH
• tabák klasifikace   genetika   mikrobiologie   MeSH
• transformace genetická MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.

• MeSH
• acinární karcinom * diagnóza   genetika   metabolismus   MeSH
• buněčné jádro patologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• imunohistochemie MeSH
• jaderné receptory - podrodina 4, skupina A, člen 2 metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinných žláz * diagnóza   genetika   patologie   MeSH
• receptory thyreoidních hormonů metabolismus   MeSH
• slinné žlázy patologie   MeSH
• steroidní receptory * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH