Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-Lx) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (Tuft1) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and β-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the Tuft1 gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.NEW & NOTEWORTHY A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (Tuft1) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the Tuft1 gene.
- MeSH
- glukosa * metabolismus MeSH
- inzulin metabolismus MeSH
- krysa rodu rattus MeSH
- metabolismus lipidů genetika MeSH
- nesmyslný kodon * genetika MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- proteom metabolismus MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Metabolism of fibronectin, the protein that plays a key role in the healing of wounds, is changed in the patients with diabetes mellitus. Fibronectin can interact with other proteins and proteoglycans and organise them to form the extracellular matrix, the basis of the granulation tissue in healing wounds. However, diabetic foot ulcers (DFUs) suffer from inadequate deposition of this protein. Degradation prevails over fibronectin synthesis in the proteolytic inflammatory environment in the ulcers. Because of the lack of fibronectin in the wound bed, the assembly of the extracellular matrix and the deposition of the granulation tissue cannot be started. A number of methods have been designed that prevents fibronectin degradation, replace lacking fibronectin or support its formation in non-healing wounds in animal models of diabetes. The aim of this article is to review the metabolism of fibronectin in DFUs and to emphasise that it would be useful to pay more attention to fibronectin matrix assembly in the ulcers when laboratory methods are translated to clinical practice.
- MeSH
- diabetes mellitus * metabolismus MeSH
- diabetická noha * terapie MeSH
- extracelulární matrix MeSH
- fibronektiny MeSH
- hojení ran MeSH
- hyperglykemie * metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Autoři předkládají didaktický přehled nejčastějších zánětlivých neinfekčních kožních onemocnění. Tento přehled není vyčerpávající, ale názorný, a to zejména z hlediska systematického přístupu k hodnocení kožní biopsie s počátečním vyhodnocením morfologického vzoru („pattern“) zánětlivého procesu, který pak usnadní další postup k určení diagnózy. K histopatologické fotografické dokumentaci je současně připojena klinická obrazová dokumentace typických primárních kožních projevů. Ta umožňuje odečítajícímu patologovi základní klinicko-patologickou korelaci, která má v dermatohistopatologii zásadní význam.
The authors present a didactic overview of the most common inflammatory non-infectious skin diseases. This overview is not exhaustive, but illustrative, especially when regarding the aspect of a systematic approach to the evaluation of skin biopsy with an initial evaluation of the morphological pattern of the inflammatory process. This will subsequently facilitate the diagnosis. Photodocumentation of typical primary skin manifestations is attached to the photomicrograph images. This enables the pathologist to make a basic clinical-pathological correlation, which is of fundamental importance in dermatopathology.
- MeSH
- biopsie * MeSH
- dermatitida * diagnóza klasifikace patologie MeSH
- diferenciální diagnóza MeSH
- kožní nemoci diagnóza klasifikace patologie MeSH
- kůže anatomie a histologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Stevens-Johnsonův syndrom a toxická epidermální nekrolýza (Lyellův syndrom) jsou vzácně se vyskytující onemocnění charakterizovaná rychlým vznikem puchýřů s následnou rozsáhlou kožní a slizniční exfoliací doprovázenou celkovými příznaky. Hlavním spouštěčem bývají ve většině případů léky, etiopatogeneze onemocnění však není zcela objasněna. Lyellův syndrom je spojen s vysokou letalitou, v průměru udávanou kolem 35 %, proto je naprosto klíčová včasná diagnostika vyžadující těsnou mezioborovou spolupráci. Diagnóza stanovená na základě klinického obrazu a podrobné farmakologické anamnézy by měla být potvrzena histopatologickým vyšetřením kožního vzorku, vč. vyšetření přímou imunofluorescencí.
Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell syndrome) are rare diseases characterized by rapid blistering followed by extensive skin and mucosal exfoliation and constitutional symptoms. In most cases, drugs are the main triggers, but the etiopathogenesis of the diseases is not fully understood. Lyell syndrome is associated with a high mortality rate, reported to be around 35%. Therefore, early diagnosis requiring close interdisciplinary cooperation is essential. The diagnosis based on the clinical picture and a detailed pharmacological history should be confirmed by histopathological examination of the skin specimen, including analysis by direct immunofluorescence.
Dermatopatologie představuje svébytnou součást patologie s bohatým přesahem do problematiky měkkých tkání či hematopatologie. Vzhledem k četnosti a rozmanitosti kožních chorob je dermatopatologie oborem obsáhlým, čítajícím stovky chorobných jednotek. Diagnostika v dermatopatologii vykazuje řadu specifik. Předkládaný článek shrnuje několik prakticky významných úskalí v dermatopatologii. Zdůrazněn je význam správného načasování a výběr vhodné lokality odběru tkáně a vliv lokální terapie na histopatologický obraz. Představeny jsou užívané chirurgické metody provedení kožní biopsie. Diskutovány jsou nejčastější incidentální nálezy a artefakty v kožní patologii. Připojena je problematika vyšetřování alopecií a vyšetření přímou imunofluorescencí. Zásadním krokem diagnostického procesu je klinicko-patologická korelace provedená jak patologem, tak následně i dermatologem. Předpokladem stanovení správné diagnózy jsou u obou specialistů znalosti přesahující rámec jejich specializace a vzájemná komunikace.
Dermatopathology is a distinct part of pathology revealing the rich association with soft tissue pathology and hematopathology. Regarding the number and diversity of the skin disorders, dermatopathology is a broad specialty encompassing hundreds of diseases. The diagnostics in dermatopathology contains a range of specific features. The article summarizes several practically important pitfalls in dermatopathology. The adequate timing and locality selection for proper sampling are emphasized. The influence of the topical therapy on the histopathological picture is debated. The frequently used surgical procedures in the skin biopsy are presented. The most frequent incidental findings and artifacts in cutaneous pathology are discussed. Problematics of the alopecia examination and direct immunofluorescence are added. Clinical-pathological correlation performed by the pathologist, and subsequently by the dermatologist, is the essential step in the diagnostic process. The knowledge transcending to the other specialty and reciprocal communication are prerequisite for the right diagnosis.
BACKGROUND: Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection. METHODS: We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies. RESULTS: Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns. CONCLUSIONS: Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIM: Gene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis. PATIENTS AND METHODS: Both paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families. RESULTS: WES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations. CONCLUSION: Our findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.
- MeSH
- adaptorové proteiny signální transdukční genetika MeSH
- cholestáza * genetika MeSH
- cytoskeletální proteiny genetika MeSH
- flavoproteiny genetika MeSH
- genotyp MeSH
- intrahepatální cholestáza * genetika diagnóza MeSH
- lidé MeSH
- mitochondriální proteiny genetika MeSH
- mutace MeSH
- protoporfyrinogenoxidasa genetika MeSH
- sekvenování exomu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Localized insulin-derived amyloidosis (LIDA) is a rare local complication of subcutaneous insulin application occurring in patients with diabetes type 1 and 2. A 45-year-old woman with an 11-year history of insulin-dependent diabetes mellitus type 1 underwent a mini-abdominoplasty and excision of a long-standing palpable mass in left hypogastric subcutaneous tissue in the area of long-term insulin application. Histopathological examination revealed insulin amyloidosis as a substrate of the mass lesion. Several months after surgery, there was a transient improvement in previously poor diabetes compensation. In addition to local allergic reactions, abscess formation, scarring, lipoatrophy/dystrophy, and lipohypertrophy, LIDA broadens the differential diagnostic spectrum of local insulin injection complications. LIDA has been described as a cause of poor glycemia compensation, probably due to the conversion of soluble insulin into insoluble amyloid fibrils, which prevents insulin from circulating in the blood and regulating glucose blood concentration. Improvement in diabetes compensation has been described in several reports, including our case. LIDA is a rare local complication of subcutaneous insulin application; accurate diagnosis and treatment have clinical consequences. Immunohistochemical or immunofluorescence distinction from other amyloid types is highly recommended.
- Publikační typ
- kazuistiky MeSH
The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
