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Renal tumors are one of the most diverse groups of tumors in pathology. Many emerging and important entities have been described recently. Here, we describe a series of renal tumors occurring in adult patients, with distinct histologic features, and with a striking resemblance to gonadal sex cord-stromal tumors. Patients were three males and three females aged 39-82 years; tumor size ranged from 0.9 to 3.6 cm. Five tumors were organ-confined, while one case had a focal perinephric invasion. No aggressive behavior was noted. Microscopically, all the tumors were composed of loose or compact tubular structures with elongated or angulated shapes. The tumor cells were cylindrical or cuboidal, with pale eosinophilic cytoplasm, irregular nuclear membranes, and ISUP/WHO grade 2-3 nuclei. The stroma showed focal or prominent collagen deposition with prominent basement membrane-like material. In all cases, the tumor cells were positive for PAX8, CD10, and vimentin and retained positivity for FH and SDHB. Cathepsin K and AMACR were variably positive. Tumors were negative for HMB45, Melan A, TFE3, SF1, inhibin, calretinin, ER, PR, CD117, OCT3/4, SALL4, ALK, and WT1. Molecular studies showed no abnormalities in TFEB, TFE3, or FH genes. In 3/4 tested cases, mutation of the NF2 gene was present. In all the tested male cases, loss of the Y chromosome was found. In the relatively short follow-up, these tumors appear to have indolent behavior. This study expands the clinicopathologic diversity of renal cell tumors by describing a series of potentially novel tumors morphologically resembling gonadal sex-stromal tumors, with negativity for sex cord-stromal markers. Potential relationship to recently described biphasic hyalinizing psammomatous renal cell carcinoma is discussed.
- MeSH
- dospělí MeSH
- gonadoblastom * MeSH
- imunohistochemie MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin * patologie MeSH
- nádory vaječníků * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory BHLH-Zip 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
Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.
Escherichia coli ST216, including those that carry blaKPC-2, blaFOX-5, blaCTX-M-15 and mcr-1, have been linked to wild and urban-adapted birds and the colonisation of hospital environments causing recalcitrant, carbapenem-resistant human infections. Here we sequenced 22 multiple-drug resistant ST216 isolates from Australian silver gull chicks sampled from Five Islands, of which 21 carried nine or more antibiotic resistance genes including blaIMP-4 (n = 21), blaTEM-1b (n = 21), aac(3)-IId (n = 20), mph(A) (n = 20), catB3 (n = 20), sul1 (n = 20), aph(3")-Ib (n = 18) and aph(6)-Id (n = 18) on FIB(K) (n = 20), HI2-ST1 (n = 11) and HI2-ST3 (n = 10) plasmids. We show that (i) all HI2 plasmids harbour blaIMP-4 in resistance regions containing In809 flanked by IS26 (HI2-ST1) or IS15DI (HI2-ST3) and diverse metal resistance genes; (ii) HI2-ST1 plasmids are highly related to plasmids reported in diverse Enterobacteriaceae sourced from humans, companion animals and wildlife; (iii) HI2 were a feature of the Australian gull isolates and were not observed in international ST216 isolates. Phylogenetic analyses identified close relationships between ST216 from Australian gull and clinical isolates from overseas. E. coli ST216 from Australian gulls harbour HI2 plasmids encoding resistance to clinically important antibiotics and metals. Our studies underscore the importance of adopting a one health approach to AMR and pathogen surveillance.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Motility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide. METHODS: We prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; < 100 mL/24 h, n = 8) or high gastric volume (HGV; > 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h. RESULTS: The findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group. CONCLUSION: All critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status. Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966 .
- MeSH
- APACHE MeSH
- ezofágus patofyziologie MeSH
- gastroezofageální reflux epidemiologie etiologie MeSH
- horní gastrointestinální trakt patofyziologie MeSH
- index tělesné hmotnosti MeSH
- kritický stav terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- manometrie metody statistika a číselné údaje MeSH
- pohybová aktivita fyziologie MeSH
- prospektivní studie MeSH
- senioři MeSH
- umělé dýchání škodlivé účinky metody statistika a číselné údaje MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: The spread of carbapenemase genes, such as blaNDM-1, in Proteus mirabilis poses a public health threat. The aim of the study was to characterize the genome and plasmids sequences of an NDM-1-positive strain (IBCRE14), which was isolated in 2019 from a catheterized patient hospitalized in Italy. Methods: Whole genome sequencing (WGS) of IBCRE14 was performed on extracted genomic DNA using Sequel I platform. Genome assembly was performed using "Microbial Assembly". Genomic analysis was conducted by uploading the contigs to ResFinder and PlasmidFinder databases from the Center for Genomic Epidemiology. Results: IBCRE14 had a genome size of 4,018,329 bp and harboured genes coding for resistance to aminoglycosides (aadA1), phenicol (cat), tetracycline (tetJ), and trimethoprim (dfrA1). A large plasmid (pIB_NDM_1) harboured antibiotic resistance genes against sulphonamide (sul1), trimethoprim (dfrA14), tetracycline (tetB), rifampicin (arr-2), aminoglycosides (aadA1, aph3-VI), and beta-lactams (blaOXA-10, blaNDM-1). Furthermore, a small plasmid (pIB_COL3M) harboured a qnrD1 gene coding for quinolone resistance. Conclusion: The ability to conjugate and the presence of a composite antibiotic resistance island suggests that pIB_NDM_1 could both acquire more resistance genes and easily disseminate. To our knowledge, this is the first report on an untypable plasmid harbouring blaNDM-1 in P. mirabilis, in Italy.
- Publikační typ
- časopisecké články MeSH
Renal epithelial cell tumors are composed of a heterogeneous group of tumors with variable morphologic, immunohistochemical, and molecular features. A "histo-molecular" approach is now an integral part of defining renal tumors, aiming to be clinically and therapeutically pertinent. Most renal epithelial tumors including the new and emerging entities have distinct molecular and genetic features which can be detected using various methods. Most renal epithelial tumors can be diagnosed easily based on pure histologic findings with or without immunohistochemical examination. Furthermore, molecular-genetic testing can be utilized to assist in arriving at an accurate diagnosis. In this review, we presented the most current knowledge concerning molecular-genetic aspects of renal epithelial neoplasms, which potentially can be used in daily diagnostic practice.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- cytomegalovirové infekce * MeSH
- Cytomegalovirus MeSH
- ganciklovir MeSH
- lidé MeSH
- valganciklovir MeSH
- viremie MeSH
- virus BK * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
Cerebellar diseases causing substantial cell loss often lead to severe functional deficits and restoration of cerebellar function is difficult. Neurotransplantation therapy could become a hopeful method, but there are still many limitations and unknown aspects. Studies in a variety of cerebellar mutant mice reflecting heterogeneity of human cerebellar degenerations show promising results as well as new problems and questions to be answered. The aim of this work was to compare the development of embryonic cerebellar grafts in adult B6CBA Lurcher and B6.BR pcd mutant mice and strain-matched healthy wild type mice. Performance in the rotarod test, graft survival, structure, and volume was examined 2 months after the transplantation or sham-operation. The grafts survived in most of the mice of all types. In both B6CBA and B6.BR wild type mice and in pcd mice, colonization of the host's cerebellum was a common finding, while in Lurcher mice, the grafts showed a low tendency to infiltrate the host's cerebellar tissue. There were no significant differences in graft volume between mutant and wild type mice. Nevertheless, B6CBA mice had smaller grafts than their B6.BR counterparts. The transplantation did not improve the performance in the rotarod test. The study showed marked differences in graft integration into the host's cerebellum in two types of cerebellar mutants, suggesting disease-specific factors influencing graft fate.
- MeSH
- modely nemocí na zvířatech * MeSH
- mozeček fyziologie transplantace MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši MeSH
- nemoci mozečku patologie terapie MeSH
- neurodegenerativní nemoci patologie terapie MeSH
- přežívání štěpu fyziologie MeSH
- transplantace fetální tkáně metody MeSH
- transplantace mozkové tkáně metody MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs. METHODS AND RESULTS: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. CONCLUSIONS: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.
- MeSH
- buněčná diferenciace MeSH
- CD antigeny genetika MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- imunohistochemie MeSH
- kadheriny genetika MeSH
- karcinoid genetika metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory ledvin genetika metabolismus patologie MeSH
- neuroendokrinní nádory genetika metabolismus patologie MeSH
- protoonkogenní proteiny genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- ztráta heterozygozity 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
- kazuistiky MeSH
AIM: To describe a group of distinct low-grade oncocytic renal tumours that demonstrate CD117 negative/cytokeratin (CK) 7-positive immunoprofile. METHODS AND RESULTS: We identified 28 such tumours from four large renal tumour archives. We performed immunohistochemistry for: CK7, CD117, PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, MOC31, CK5/6, p63, HMB45, melan A, CD15 and FH. In 14 cases we performed array CGH, with a successful result in nine cases. Median patient age was 66 years (range 49-78 years) with a male-to-female ratio of 1:1.8. Median tumour size was 3 cm (range 1.1-13.5 cm). All were single tumours, solid and tan-brown, without a syndromic association. On microscopy, all cases showed solid and compact nested growth. There were frequent areas of oedematous stroma with loosely arranged cells. The tumour cells had oncocytic cytoplasm with uniformly round to oval nuclei, but without significant irregularities, and showed only focal perinuclear halos. Negative CD117 and positive CK7 reactivity were present in all cases (in two cases there was focal and very weak CD117 reactivity). Uniform reactivity was found for PAX8, AE1/AE3, e-cadherin, BerEP4 and MOC31. Negative stains included CA9, CK20, vimentin, CK5/6, p63, HMB45, Melan A and CD15. CD10 and AMACR were either negative or focally positive; FH was retained. On array CGH, there were frequent deletions at 19p13.3 (seven of nine), 1p36.33 (five of nine) and 19q13.11 (four of nine); disomic status was found in two of nine cases. On follow-up (mean 31.8 months, range 1-118), all patients were alive with no disease progression. CONCLUSION: Low-grade oncocytic tumours that are CD117-negative/CK7-positive demonstrate consistent and readily recognisable morphology, immunoprofile and indolent behaviour.
- MeSH
- imunohistochemie MeSH
- keratin-7 analýza biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin patologie MeSH
- oxyfilní adenom patologie MeSH
- protoonkogenní proteiny c-kit analýza biosyntéza MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
