Результаты поиска

Acetylcholinesterases from Elapidae snake venoms: biochemical, immunological and enzymatic characterization.

We analyzed 45 batches of venom from 20 different species belonging to 11 genera from the 3 main families of venomous snakes (Elapidae, Vipe … hE of all venoms have similar turnovers (6000 to 8000 s(-1)) which are clearly higher than those of Torpedo and mammalian enzymes but lower than that of Electrophorus. AChEs from the venom of elapid snakes of the Bungarus, Naja, Ophiophagus and Haemacatus genera were purified by affinity chromatography. SDS-PAGE analysis and sucrose gradient centrifugatio …

Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia.

The muscle chloride channel CIC-1 regulates the electric excitability of the skeletal muscle membrane. Mutations in the gene encoding this chloride channel (CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's disease, GM) and autosomal dominant myotonia congenita (Thomsen's disease, MC). We now show that the protein-coding sequence of the CLCN1 gene is organized into 23 exons. The CIC-1 upstream region contains a canonical TATA box, several consensus binding sites for myogenic transcription factors and two other putative regulator

Xenoxins, a family of peptides from dorsal gland secretion of Xenopus laevis related to snake venom cytotoxins and neurotoxins.

Three new, highly similar peptides from the skin secretion of Xenopus laevis have been purified and analyzed by mass spectrometry and Edman degradation. The 66-amino-acid peptides, termed xenoxin-1, -2, and -3, contain 8 cysteines and show similarity to snake venom cytotoxins and short neurotoxins. Assignment of two out of four disulfide bonds suggests a tertiary structure similar to that of cytotoxins and short neurotoxins. A cDNA encoding pre-xenoxin-1 was isolated from a X. laevis skin cDNA library. The nucleotide sequence predicts the synthesis of a precursor with a signal peptide followed

Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism.

Spirolide and gymnodimine macrocyclic imine phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Analysis of 13-desmethyl spirolide C and gymnodimine A by binding and voltage-clamp recordings on muscle-type alpha1(2)betagammadelta and neuronal alpha3beta2 and alpha4beta2 nicotinic acetylcholine receptors reveals subnanomolar affinities, potent antagonism, and limited subtype selectivity. Their binding to acetylcholine-binding proteins (AChBP), as soluble receptor surrogates, exhibits picomolar affinities governed by diffusion-li

Interactions of delta-conotoxins with alkaloid neurotoxins reveal differences between the silent and effective binding sites on voltage-sensitive sodium channels.

The delta-conotoxin-TxVIA from Conus textile (delta TxVIA) is a mollusk-specific conotoxin that slows sodium channel inactivation exclusively in mollusk neuronal membranes but reveals high-affinity binding to both mollusk (effective binding) and rat brain (silent binding) neuronal membranes, despite not having any toxic effect in vertebrates in vivo and in vitro. Using binding studies with radioactive delta TxVIA we demonstrate that a different mollusk-specific conotoxin, delta-conotoxin-GmVIA from the venom of Conus gloriamaris, possesses "silent" and effective binding properties in rat brain

Motor neuron pathology in CANVAS due to RFC1 expansions.

CANVAS caused by RFC1 biallelic expansions is a major cause of inherited sensory neuronopathy. Detection of RFC1 expansion is challenging an … rn at the lumbar level. The cerebellum showed mild depletion of Purkinje cells, with empty baskets, torpedoes, and astrogliosis characterized by a disorganization of the Bergmann's radial glia. We found neuronal loss in the vagal nucleus. The pars compacta of the substantia nigra was depleted, with widespread Lewy bodies in the locus coeruleus, substantia …

Hysteria after Charcot: back to the future.

The studies on hysteria and hypnotism probably constitute the most important long-term work of Jean-Martin Charcot and his school, starting … Ballet, Achille Souques). Babinski's pupil Clovis Vincent developed a treatment called torpillage (torpedoing) against war hysteria, associating painful galvanic current discharges with 'persuasion', but this was dismissed after the soldiers, considering it as torture, rebelled. After World War I, the neurological and psychiatric interest in hysteria aga …

Prion protein deposition and abnormal synaptic protein expression in the cerebellum in Creutzfeldt-Jakob disease.

Prion protein (PrP(C)) is a cell membrane-anchored glycoprotein, which is replaced by a pathogenic protease-resistant, beta-sheet-containing … se, but reduced expression was inconstant in the molecular layer. Synaptophysin accumulated in axon torpedoes, thus indicating abnormal axon transport. Expression of synaptic proteins was relatively preserved in the dentate nucleus, although synaptophysin immunohistochemistry disclosed large coarse pericellular terminals in Creutzfeldt-Jakob disease, inst …

Effects of some immunosuppressive procedures on myasthenia gravis.

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the fol … Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin bind …

Nicotinic acetylcholine receptors in health and disease.

Nicotinic acetylcholine receptors (AChRs) are a family of acetylcholine-gated cation channels that form the predominant excitatory neurotransmitter receptors on muscles and nerves in the peripheral nervous system. AChRs are also expressed on neurons in lower amounts throughout the central nervous system. AChRs are even being reported on unexpected cell types such as keratinocytes. Structures of these AChRs are being determined with increasing precision, but functions of some orphan subunits are just beginning to be established. Functional roles for postsynaptic AChRs in muscle are well known,

Matching asymmetry of tremor with asymmetry of postmortem cerebellar hemispheric changes in essential tremor.

Although the number of postmortem studies in essential tremor (ET) has grown in recent years, clinical-pathological correlations remain limi … andard tissue block of both right and left neocerebellums to quantify Purkinje cell linear density, torpedo counts, and a group of previously described changes in Purkinje cell axonal shape (thickened axonal profiles) and connectivity (axon recurrent collaterals, axonal branching, terminal axonal sprouting, arciform axons, extent of recurrent collateral p …

On the initial trigger of myasthenia gravis and suppression of the disease by antibodies against the MHC peptide region involved in the presentation of a pathogenic T-cell epitope.

Myasthenia gravis (MG) is a disabling autoimmune disease caused by autoantibodies (auto-Abs) against the self-acetylcholine receptor (AChR). … G (experimental autoimmune MG, EAMG) can be induced in C57BL/6 (B6, H-2b) mice by immunization with Torpedo californica (t) AChR. A mutant mouse of B6, B6.C-H-2bm12 (bm12), which has three amino acid changes (at residues 67, 70, and 71) in the I-A beta(b) subunit, is resistant to EAMG development. Recently, we showed that region 62-76 of I-A beta(b), whic …

Monocyte-macrophage SAMHD1 alleviates EAMG by modulating the cGAS-STING pathway.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder whose pathogenesis has not been fully elucidated but is primarily associated wi … ETHODS: Experimental autoimmune myasthenia gravis (EAMG) rat models were established using purified torpedo acetylcholine receptor (AChR). Peripheral blood samples from MG patients and healthy controls were collected for clinical validation. Single-cell RNA sequencing was performed on peripheral whole blood from EAMG and control rats, as well as on human …

Generation of acetylcholine receptor-specific human T cell lines using heterobifunctional antibody-targeted antigen presentation.

Characterizing AChR-specific T lymphocyte clones is an important step towards the ability to induce antigen-specific tolerance in myasthenia gravis (MG). However, the limited supply of relatively inefficient autologous antigen presenting cells (APCs) makes establishing AChR-specific T lymphocyte lines difficult. In this study we targeted AChR to autologous surface IgM+ (sIgM+) APCs using heterobifunctional antibodies (bi-Ab) consisting of anti-sIgM linked to anti-AChR antibodies. FACScan analysis and whole cell-based radioimmunoassay (RIA) showed binding of bi-Ab/AChR conjugates to sIgM+ APCs.

Transsplenic tract closure after transsplenic portalvenous access using gelfoam-based tract plugging.

BACKGROUND: To assess the feasibility and safety of a gelfoam torpedo plugging technique for embolization of the transsplenic access channel in adult patients following transvenous portal vein interventions. MATERIALS AND METHODS: Between 09/2016 and 08/2021, an ultrasound guided transsplenic portalvenous access (TSPVA) was established in twenty-four adult patients with a 21-G needle and 4-F microsheath under ultrasound guidance. Afterwards, sheaths ranging from 4-F to 8-F were inserted as needed for the procedure. Following portal vein intervention, the splenic access tract was embolized wit…

A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.

OBJECTIVES: Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases. METHODS: A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and obse

Совпадение в полном тексте источника
… patients who had an IR to ≥1 DMARDs, including anti-TNF agents. 15 Intravenous TCZ was more effective than placebo in reducing signs and symptoms in patients with RA who failed to respond adequately to DMARD therapy, among them approximately 38% in both groups with previous use of anti-TNF agents. 14 The TORPEDO … Torpedo study: a study on rapid effect of tocilizumab in patients with rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or anti-TNF. Available: https://clinicaltrials.gov/ct2/show/NCT00977106 [Accessed 10 Nov 2020]. 40. …

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribu

In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

Invited Lectures : Overviews Purinergic signalling: past, present and future.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Research Communications of the 26th ECVIM‐CA Congress

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.