BACKGROUND: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. METHODS: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. RESULTS: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). CONCLUSIONS: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

• MeSH
• COVID-19 * mortalita   genetika   MeSH
• dospělí MeSH
• intersticiální nefritida genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 1 * krev   MeSH
• mutace * MeSH
• registrace MeSH
• SARS-CoV-2 genetika   MeSH
• senioři MeSH
• uromodulin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

The publication focuses on methods of RT-qPCR testing of viral respiratory diseases, for example COVID-19. Intended for professional public.

• MeSH
• infekce dýchací soustavy diagnóza   MeSH
• polymerázová řetězová reakce metody   MeSH
• testování na COVID-19 metody   MeSH
• virologie MeSH
• virové nemoci diagnóza   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• pneumologie a ftizeologie
• diagnostika

The inability to predict the evolution of the COVID-19 epidemic hampered abilities to respond to the crisis effectively. The cycle threshold (Ct) from the standard SARS-CoV-2 quantitative reverse transcription-PCR (RT-qPCR) clinical assay is inversely proportional to the amount of SARS-CoV-2 RNA in the sample. We were interested to see if population Ct values could predict future increases in COVID-19 cases as well as subgroups that would be more likely to be affected. This information would have been extremely helpful early in the COVID-19 epidemic. We therefore conducted a retrospective analysis of demographic data and Ct values from 2,076,887 nasopharyngeal swab RT-qPCR tests that were performed at a single diagnostic laboratory in the Czech Republic from April 2020 to April 2022 and from 221,671 tests that were performed as a part of a mandatory school surveillance testing program from March 2021 to March 2022. We found that Ct values could be helpful predictive tools in the real-time management of viral epidemics. First, early measurement of Ct values would have indicated the low viral load in children, equivalent viral load in males and females, and higher viral load in older individuals. Second, rising or falling median Ct values and differences in Ct distribution indicated changes in the transmission in the population. Third, monitoring Ct values and positivity rates would have provided early evidence as to whether prevention measures are effective. Health system authorities should thus consider collecting weekly median Ct values of positively tested samples from major diagnostic laboratories for regional epidemic surveillance.

• MeSH
• COVID-19 * epidemiologie   diagnóza   MeSH
• dítě MeSH
• lidé MeSH
• retrospektivní studie MeSH
• RNA virová genetika   analýza   MeSH
• SARS-CoV-2 * genetika   MeSH
• senioři MeSH
• virová nálož MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Osobní vzpomínky autora na laboratorní výzkum a PCR testování COVID-19. Určeno široké veřejnosti.

• MeSH
• COVID-19 dějiny   MeSH
• dějiny 21. století MeSH
• klinické laboratoře dějiny   MeSH
• pracovníci laboratoře dějiny   MeSH
• testování na COVID-19 dějiny   MeSH
• Check Tag
• dějiny 21. století MeSH
• Publikační typ
• osobní vyprávění MeSH
• populární práce MeSH
• Geografické názvy
• Česká republika MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví
• experimentální medicína

Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.

• MeSH
• amyloidóza * komplikace   MeSH
• lidé MeSH
• mutace MeSH
• promotorové oblasti (genetika) MeSH
• sérový amyloid A genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Identification of the content of asialotransferrin in the cerebrospinal fluid is a diagnostic method for childhood-onset ataxia and central nervous system hypomyelination (CACH), also known as vanishing white matter disease (VWM), and also for other types of CNS disorders. METHODS: In our work, we have determined the value of the ratio of the asialo form of transferrin to the total transferrin in the CSF using the commercially used Variant(TM) Bio-Rad system for the determination of carbohydrate-deficient transferrin (CDT) in serum. The peak corresponding to the asialo form of transferrin was identified with electrophoresis with subsequent immunofixation and mass spectrometry (MALDI-TOF/TOF). RESULTS: The intra-assay and inter-assay variations of the asialotransferrin value in CSF were 6.8% and 10.2%, respectively. Analysing CSF samples of 60 subjects (23 men aged 22-68 years and 37 women aged 18-77 years) with normal transferrin values and normal cytology as well as biochemistry parameters in the cerebrospinal fluid, and without apparent signs of neurological disorders, we have found the presence of 25.2 +/- 8.2% asialotransferrin. CONCLUSION: Except for the need to obtain approximately 1.5 mL of cerebrospinal fluid and a tenfold concentrating of the sample, there is no need to conduct any modifications of the preparation procedure for the analytic sample and chromatographic separation normally used for serum samples. The HPLC method of asialotransferrin determination in CSF provides clinically useful results.

• MeSH
• asialoglykoproteiny analýza   MeSH
• dospělí MeSH
• imunoelektroforéza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• protein - isoformy analýza   krev   MeSH
• senioři MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• tandemová hmotnostní spektrometrie MeSH
• transferin analogy a deriváty   analýza   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function.

• MeSH
• Caenorhabditis elegans chemie   metabolismus   MeSH
• chromatografie kapalinová metody   MeSH
• financování organizované MeSH
• proteiny Caenorhabditis elegans analýza   metabolismus   MeSH
• proteom analýza   metabolismus   MeSH
• proteomika metody   MeSH
• receptory cytoplazmatické a nukleární fyziologie   genetika   MeSH
• vývoj svalů genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• MeSH
• buněčné jádro metabolismus   MeSH
• Caenorhabditis elegans genetika   metabolismus   růst a vývoj   MeSH
• dominantní geny MeSH
• embryo nesavčí cytologie   embryologie   metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• financování organizované MeSH
• geny helmintů genetika   MeSH
• larva metabolismus   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• receptory cytoplazmatické a nukleární genetika   metabolismus   MeSH
• specificita protilátek MeSH
• vývojová regulace genové exprese MeSH

• MeSH
• Caenorhabditis elegans cytologie   genetika   MeSH
• finanční podpora výzkumu jako téma MeSH
• genetická transkripce imunologie   MeSH
• inhibitory apoptózy analýza   genetika   MeSH
• lidé MeSH
• mikročipová analýza metody   využití   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   využití   MeSH
• RNA interference fyziologie   MeSH
• savci genetika   MeSH
• vývojová regulace genové exprese genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• astrocytom enzymologie   genetika   MeSH
• buněčné jádro metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• glióza metabolismus   MeSH
• histondeacetylasy genetika   metabolismus   MeSH
• konfokální mikroskopie MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• nádory mozku enzymologie   genetika   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• sekvence aminokyselin MeSH
• Check Tag
• lidé MeSH