Time-resolved NMR
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Východiska: Oční nádory jsou pohyblivým cílem léčby, ale v literatuře není žádná zmínka o radioterapii s monitorováním v reálném čase. Případ: Žena ve věku 54 let s metastazujícím karcinomem prsu byla odeslána k léčbě diplopie v důsledku choroidální metastázy po hipokampus šetřícím celomozkovém ozáření. Vzhledem k tomu, že zraková ostrost byla zachována a očekávalo se dlouhodobé přežití, byla provedena MR-řízená radioterapie s modulovanou intenzitou v reálném čase (36 Gy ve 20 frakcích). Během léčby ani během následného ročního sledování se nevyskytly žádné nežádoucí příhody. Pacientčina diplopie ustoupila a během sledovacího období nebyla pozorována žádná recidiva nádoru choroidey. Závěr: MRI-řízená radioterapie může být bezpečnou a účinnou léčbou choroidálních metastáz po hipokampus šetřícím celomozkovém ozáření.
Background: Eye tumors are moving targets, but there have been no reports of radiation therapy with real-time monitoring. Case: A 54-year-old woman with metastatic breast cancer was referred for treatment of diplopia due to choroidal metastasis after hippocampal avoiding whole brain radiotherapy. Since visual acuity was preserved and long-term survival was expected, real-time MRI-guided intensity-modulated radiation therapy (36 Gy in 20 fractions) was performed. No adverse events occurred during treatment or during the subsequent one-year follow-up period. The patient‘s diplopia resolved and no choroidal recurrence was observed during the follow-up period. Conclusion: MRI-guided radiation therapy may be a safe and effective treatment for choroidal metastases after hippocampal avoiding whole brain radiotherapy.
BACKGROUND: Stroke-like syndrome is defined as a rare, delayed complication of brain oncotherapy. Cases with more favorable brain cancer diagnoses and longer life expectancy have been previously reported, but here we present, for the first time, three long-term survivors of glioblastoma with stroke-like syndromes. METHODS AND RESULTS: Three young or middle-aged patients underwent tumor resection and chemoradiotherapy. They received regular clinical and imaging follow-up with stable neurological status and no signs of tumor recurrence. They exhibited varied signs and symptoms (motor and sensory deficits, aphasia, memory and cognitive disorders, seizures, and headache) accompanied by imaging abnormalities. Stroke-like syndromes developed within 2-5 days and resolved in 2-6 weeks. Diffusion-weighted MRI and T2 brain perfusion abnormalities were demonstrated in all patients. In addition, there was focal T1 MRI contrast enhancement due to blood-brain barrier disruption. In addition to tumor recurrence, classic stroke, encephalitis, metabolic and mitochondrial disorders, and post-seizure swelling should be excluded. The imaging indicated intensive MRI scanning and symptomatic medication (steroids supplemented by antiepileptics, vasoactive agents, etc.) for judicious management. With respect to the course, an invasive procedure was still considered an option. CONCLUSION: All stroke-like syndromes are diagnoses of exclusion. To avoid misinterpretation of imaging findings as glioblastoma recurrence and avert recall oncotherapy or redundant interventions, better understanding of delayed complications of brain tumor therapy is crucial.
- MeSH
- cévní mozková příhoda * komplikace etiologie MeSH
- glioblastom * radioterapie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- magnetická rezonanční tomografie metody MeSH
- nádory mozku * komplikace patologie terapie MeSH
- syndrom MeSH
- záchvaty etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
We recently showed that Saccharomyces cerevisiae telomeric DNA can fold into an unprecedented pseudocircular G-hairpin (PGH) structure. However, the formation of PGHs in the context of extended sequences, which is a prerequisite for their function in vivo and their applications in biotechnology, has not been elucidated. Here, we show that despite its 'circular' nature, PGHs tolerate single-stranded (ss) protrusions. High-resolution NMR structure of a novel member of PGH family reveals the atomistic details on a junction between ssDNA and PGH unit. Identification of new sequences capable of folding into one of the two forms of PGH helped in defining minimal sequence requirements for their formation. Our time-resolved NMR data indicate a possibility that PGHs fold via a complex kinetic partitioning mechanism and suggests the existence of K+ ion-dependent PGH folding intermediates. The data not only provide an explanation of cation-type-dependent formation of PGHs, but also explain the unusually large hysteresis between PGH melting and annealing noted in our previous study. Our findings have important implications for DNA biology and nanotechnology. Overrepresentation of sequences able to form PGHs in the evolutionary-conserved regions of the human genome implies their functionally important biological role(s).
- MeSH
- konformace nukleové kyseliny MeSH
- kruhová DNA chemie MeSH
- molekulární modely MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- nukleotidové motivy MeSH
- párování bází MeSH
- Saccharomyces cerevisiae genetika MeSH
- stereoizomerie MeSH
- telomery chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Diabetic striatopathy is a rare condition characterized by unilateral hemichorea and/or hemiballismus in the settings of uncontrolled nonketotic diabetes mellitus. Imaging studies usually reveal striatal abnormality - subtle hyperdensity on CT and T1 hyperintensity on MRI. The resolution of clinical symptoms is prompt when optimal glycaemic control is achieved. CASE REPORT: We present the case of a 90-year-old male who came to our attention for acute involuntary choreiform movements of his left-sided extremities lasting two-weeks. Apart from that neurological examination was unremarkable. His medical history included hypertension, atrial fibrillation, previous stroke with no residual disability and poorly controlled type 2 diabetes mellitus on metformin treatment. There was no history of movement disorders or exposure to neuroleptics. His glucose level on admission was 512.6 mg/dL, glycated hemoglobin was 14%. CT scan of the head demonstrated an abnormally increased intensity within the right striatum. Treatment consisted of symptomatic treatment of chorea and improvement of blood glucose control. Tiapride was started with a dose of 100 mg 4 times a day. The patient was initiated on intensive insulin therapy which included insulin glargine 10 units every evening and 12 units of insulin glulisine 3 times a day with meals. Abnormal movements resolved after normoglycemia was achieved approximately 7 days after admission. Though striatal hyperdensity was still present at follow-up CT scan after 10 days, it was less pronounced. CONCLUSION: Diabetic striatopathy is a rare but treatable disorder and should be considered in patients with poorly controlled diabetes who present with hemichorea.
- MeSH
- cévní mozková příhoda * MeSH
- chorea * diagnostické zobrazování farmakoterapie MeSH
- diabetes mellitus 2. typu * MeSH
- hyperglykemie * komplikace farmakoterapie MeSH
- ketosy MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- pyrazoly MeSH
- pyridony MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Signal enhancements of up to two orders of magnitude in protein NMR can be achieved by employing HDO as a vector to introduce hyperpolarization into folded or intrinsically disordered proteins. In this approach, hyperpolarized HDO produced by dissolution-dynamic nuclear polarization (D-DNP) is mixed with a protein solution waiting in a high-field NMR spectrometer, whereupon amide proton exchange and nuclear Overhauser effects (NOE) transfer hyperpolarization to the protein and enable acquisition of a signal-enhanced high-resolution spectrum. To date, the use of this strategy has been limited to 1D and 1H-15N 2D correlation experiments. Here we introduce 2D 13C-detected D-DNP, to reduce exchange-induced broadening and other relaxation penalties that can adversely affect proton-detected D-DNP experiments. We also introduce hyperpolarized 3D spectroscopy, opening the possibility of D-DNP studies of larger proteins and IDPs, where assignment and residue-specific investigation may be impeded by spectral crowding. The signal enhancements obtained depend in particular on the rates of chemical and magnetic exchange of the observed residues, thus resulting in non-uniform 'hyperpolarization-selective' signal enhancements. The resulting spectral sparsity, however, makes it possible to resolve and monitor individual amino acids in IDPs of over 200 residues at acquisition times of just over a minute. We apply the proposed experiments to two model systems: the compactly folded protein ubiquitin, and the intrinsically disordered protein (IDP) osteopontin (OPN).
- MeSH
- lidé MeSH
- nukleární magnetická rezonance biomolekulární * MeSH
- osteopontin chemie MeSH
- ubikvitin chemie MeSH
- vnitřně neuspořádané proteiny chemie MeSH
- voda chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE: To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE: Prospective technical development. POPULATION: Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT: Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS: SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS: T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION: PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.
- MeSH
- dospělí MeSH
- fantomy radiodiagnostické MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie * MeSH
- omega-3 mastné kyseliny chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- počítačová simulace MeSH
- podkožní tuk diagnostické zobrazování MeSH
- poměr signál - šum MeSH
- prospektivní studie MeSH
- senioři MeSH
- zdraví dobrovolníci pro lékařské studie 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
OBJECTIVE: Cysts of the Cavum septi pellucidi (CSP), cavum vergae (CV) and cavum veli interpositi (CVI) are anterior midline intracranial findings which are typically incidental - only rarely do we encounter symptomatic cysts of this type. Only a quite small number of these cysts series have been published, controversies regarding optimal management still exist. PATIENTS AND METHODS: This is a retrospective study of 10 patients treated at 2 clinics between 2002-2018. 9 patients underwent surgery and 1 is under long-term monitoring. Apart from demographic data, the study analyzed symptoms, cyst size and progression over time, ventricle size, complications, and treatment modality. RESULTS: CSP with CV was found in 8 cases with 1 case each of CSP and CVI. The study comprised 6 men and 4 women, including 4 children. The mean follow-up time was 43.4 months. The average cyst size was 20.4 mm in CSP and 19.8 mm in CV; the CVI was 33 mm. Headache was most commonly reported (70%) followed by behavioral disturbance (30%). Disturbance in memory, psychomotor development, school performance, visual acuity, and vomiting was variously noted in 20%. The prevailing symptom was headache in adults and behavioral and autonomic disturbance in children. Postoperatively, cysts had reduced by an average of 44.3% while the ventricles remained unchanged. Symptoms resolved in all cases with residual problems in patients presenting with memory loss. No complications were noted. CONCLUSION: Endoscopic fenestration is the method of choice in the treatment of symptomatic midline cysts. We recommend that any further research focuses on precisely establishing their clinical presentation, particularly neuropsychological symptoms.
- MeSH
- cysty centrálního nervového systému diagnostické zobrazování patofyziologie chirurgie MeSH
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory mozku diagnostické zobrazování patofyziologie chirurgie MeSH
- neuroendoskopie metody MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- senioři MeSH
- septum pellucidum diagnostické zobrazování chirurgie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- multicentrická studie MeSH
Astragalus is a very interesting plant genus, well-known for its content of flavonoids, triterpenes and polysaccharides. Its secondary metabolites are described as biologically active compounds showing several activities, e.g., immunomodulating, antibacterial, antiviral and hepatoprotective. This inspired us to analyze the Bulgarian endemic A. aitosensis (Ivanisch.) to obtain deeper information about its phenolic components. We used extensive chromatographic separation of A. aitosensis extract to obtain seven phenolic compounds (1-7), which were identified using combined LC-MS and NMR spectral studies. The 1D and 2D NMR analyses and HR-MS allowed us to resolve the structures of known compounds 5-7 as isorhamnetin-3-O-robinobioside, isorhamnetin-3-O-(2,6-di-O-α-rhamno-pyranosyl-β-galactopyranoside), and alangiflavoside, respectively, and further comparison of these spectral data with available literature helped us with structural analysis of newly described flavonoid glycosides 1-4. These were described in plant source for the first time.
- MeSH
- Astragalus chemie MeSH
- chromatografie kapalinová MeSH
- fenoly chemie izolace a purifikace MeSH
- flavonoidy chemie izolace a purifikace MeSH
- glykosidy chemie klasifikace izolace a purifikace MeSH
- hmotnostní spektrometrie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- triterpeny chemie MeSH
- Publikační typ
- časopisecké články MeSH
Earlier experiments, using 31 P-NMR and time-resolved merocyanine fluorescence spectroscopy, have shown that isolated intact, fully functional plant thylakoid membranes, in addition to the bilayer phase, contain three non-bilayer (or non-lamellar) lipid phases. It has also been shown that the lipid polymorphism of thylakoid membranes can be characterized by remarkable plasticity, i.e. by significant variations in 31 P-NMR signatures. However, changes in the lipid-phase behaviour of thylakoids could not be assigned to changes in the overall membrane organization and the photosynthetic activity, as tested by circular dichroism and 77 K fluorescence emission spectroscopy and the magnitude of the variable fluorescence of photosystem II, which all showed only marginal variations. In this work, we investigated in more detail the temporal stability of the different lipid phases by recording 31 P-NMR spectra on isolated thylakoid membranes that were suspended in sorbitol- or NaCl-based media. We observed, at 5°C during 8 h in the dark, substantial gradual enhancement of the isotropic lipid phases and diminishment of the bilayer phase in the sorbitol-based medium. These changes compared well with the gradually increasing membrane permeability, as testified by the gradual acceleration of the decay of flash-induced electrochromic absorption changes and characteristic changes in the kinetics of fast chlorophyll a-fluorescence transients; all variations were much less pronounced in the NaCl-based medium. These observations suggest that non-bilayer lipids and non-lamellar lipid phases play significant roles in the structural dynamics and functional plasticity of thylakoid membranes.
Chloroplast thylakoid membranes contain virtually all components of the energy-converting photosynthetic machinery. Their energized state, driving ATP synthesis, is enabled by the bilayer organization of the membrane. However, their most abundant lipid species is a non-bilayer-forming lipid, monogalactosyl-diacylglycerol; the role of lipid polymorphism in these membranes is poorly understood. Earlier 31P-NMR experiments revealed the coexistence of a bilayer and a non-bilayer, isotropic lipid phase in spinach thylakoids. Packing of lipid molecules, tested by fluorescence spectroscopy of the lipophilic dye, merocyanine-540 (MC540), also displayed heterogeneity. Now, our 31P-NMR experiments on spinach thylakoids uncover the presence of a bilayer and three non-bilayer lipid phases; time-resolved fluorescence spectroscopy of MC540 also reveals the presence of multiple lipidic environments. It is also shown by 31P-NMR that: (i) some lipid phases are sensitive to the osmolarity and ionic strength of the medium, (ii) a lipid phase can be modulated by catalytic hydrogenation of fatty acids and (iii) a marked increase of one of the non-bilayer phases upon lowering the pH of the medium is observed. These data provide additional experimental evidence for the polymorphism of lipid phases in thylakoids and suggest that non-bilayer phases play an active role in the structural dynamics of thylakoid membranes.
