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Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor activity but does not alter minimum alveolar anesthetic concentration.

UNLABELLED: A naturally occurring brain lipid, cis-9,10-octadeceamide--oleamide (OA), is found in increased concentrations in the cerebrospinal fluid of sleep-deprived cats, which suggests that it may be an endogenous sleep-inducing substance. We studied the effects of this fatty-acid derivative on the function of cloned gamma-aminobutyric acid (GABA(A)) receptors expressed in Xenopus oocytes. Oocytes were injected with cRNA synthesized in vitro to express simple GABA(A) receptors (alpha1beta1, alpha3beta1, alpha5beta1, and alpha1beta2 subunit combinations) and receptors in which the GABA-indu

Safety of arylsulfatase A overexpression for gene therapy of metachromatic leukodystrophy.

Successful gene therapy approaches for metachromatic leukodystrophy (MLD), based either on hematopoietic stem/progenitor cells (HSPCs) or direct central nervous system (CNS) gene transfer, highlighted a requirement for high levels of arylsulfatase A (ARSA) expression to achieve correction of disease manifestations in the mouse model. Full assessment of the safety of ARSA expression above physiological levels thus represents a prerequisite for clinical translation of these approaches. Here, using lentiviral vectors (LVs), we generated two relevant models for the stringent evaluation of the cons

Carbohydrates as antigenic determinants of tumor-associated antigens recognized by monoclonal anti-tumor antibodies produced in a syngeneic system.

Two monoclonal antibodies (KH-1 and KH-2) against a transplanted fibrosarcoma (KMT-17) in WKA rats were produced by fusing a mouse myeloma (P3-X63-Ag8.653) with spleen cells from syngeneic rats hyperimmunized with KMT-17. Both antibodies showed complement-dependent cytotoxicity against KMT-17. By absorption of cytotoxicity, KH-1 reacted with homologous tumor, other syngeneic fibrosarcomas (KMT-80 and KMT-75), and lung and kidney from normal rats. However, KH-2 reacted with many kinds of tumors and various normal tissues. Antigen specificity was tested by complement fixation and/or solid-phase

Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis.

The side effects of current immunosuppressive drugs have impeded the development of therapies for immune diseases. Selective regulation of STAT signaling is an attractive strategy for treating immune disorders. In this study, we used a small-molecule compound to explore possible means of targeting STAT1 for the treatment of Th1-mediated inflammation. Selective regulation of STAT1 signaling in T cells from C57BL/6 mice was accomplished using fusaruside, a small-molecule compound that triggers the tyrosine phosphorylation of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2). The i

Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene.

Metachromatic leukodystrophy (MLD) rarely has its clinical onset in young adults, with a combination of cognitive and behavioural symptoms and peripheral neuropathy. Here we present an exceptional case with very late onset at 42 years of age and no clinical or neurophysiological sign of peripheral neuropathy. Molecular analysis revealed compound heterozygosity for two novel missense mutations affecting conserved residues in the arylsulphatase A (ASA) sulphatase and carboxyterminal domains, resulting in an 89% loss of enzymatic activity. This case indicates that MLD needs to be considered in th

Arylsulfatase A Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy.

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder resulting from a functional deficiency of arylsulfatase A (ARSA), an enzyme that catalyzes desulfation of 3-O-sulfogalactosylceramide (sulfatide). Lack of active ARSA leads to the accumulation of sulfatide in oligodendrocytes, Schwann cells and some neurons and triggers progressive demyelination, the neuropathological hallmark of MLD. Several therapeutic approaches have been explored, including enzyme replacement, autologous hematopoietic stem cell-based gene therapy, intracerebral gene therapy or cell-based gene del

Ex vivo cell-mediated gene therapy for metachromatic leukodystrophy using neurospheres.

Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the gene encoding the lysosomal enzyme arylsulfatase A (ASA). In MLD, accumulation of the substrate, sulfated glycoprotein, in the central and peripheral nervous systems results in progressive motor and mental deterioration. Neural progenitor cells are thought to be useful for cell replacement therapy and for cell-mediated gene therapy in neurodegenerative diseases. In the present study, we examined the feasibility of ex vivo gene therapy for MLD using neural progenitor cells. Neural progenitor cells (n

[Carbon monoxide contamination: an environmental health problem].

Carbon monoxide is considered to be a major factor contaminating earth's atmosphere. The main sources producing this contamination are cars using gasoline or diesel fuel and industrial processes using carbon compounds; these two are responsible for 80% of carbon monoxide being emitted to the atmosphere. This substance has a well-known toxic effect on human beings and its acute poisonous effects (including death) have been widely studied; however, its long-term chronic effects are still not known. During the last few years, experimental research on animals and studies of human epidemiology have

Clinical and biochemical study of 29 Brazilian patients with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a lysosomal disorder caused by arylsulfatase A (ARSA) deficiency. It is classified into three forms according to the age of onset of symptoms (late infantile, juvenile, and adult). We carried out a cross-sectional and retrospective study, which aimed to determine the epidemiological, clinical, and biochemical profile of MLD patients from a national reference center for Inborn Errors of Metabolism in Brazil. Twenty-nine patients (male, 17) agreed to participate in the study (late infantile form: 22; juvenile form: 4; adult form: 1; asymptomatic: 2). Mean ag

Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA). Clinically, the disease is heterogeneous with respect to the age of onset, affection of peripheral and central nervous systems, and progression. OBJECTIVES: To analyze mutations in the ARSA gene of a patient with adult-onset MLD with no signs of peripheral polyneuropathy and to emphasize the clinical, neuroradiologic, neuropathologic, and genetic features of the disease. DESIGN: Case study of a patient clinically presenting with rapidly progressive dementia and be

Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A.

Variant late infantile neuronal ceroid lipofuscinosis, a lysosomal storage disorder characterized by progressive mental deterioration and blindness, is caused by mutations in a polytopic membrane protein (CLN6) with unknown intracellular localization and function. In this study, transient transfection of BHK21 cells with CLN6 cDNA and immunoblot analysis using peptide-specific CLN6 antibodies demonstrated the expression of a approximately 27-kDa protein that does not undergo proteolytic processing. Cross-linking experiments revealed the presence of CLN6 dimers. Using double immunofluorescence

Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy.

Allogeneic fetal-derived human neural stem cells (hfNSCs) that are under clinical evaluation for several neurodegenerative diseases display a favorable safety profile, but require immunosuppression upon transplantation in patients. Neural progenitors derived from patient-specific induced pluripotent stem cells (iPSCs) may be relevant for autologous ex vivo gene-therapy applications to treat genetic diseases with unmet medical need. In this scenario, obtaining iPSC-derived neural stem cells (NSCs) showing a reliable "NSC signature" is mandatory. Here, we generated human iPSC (hiPSC) clones via

Anti-Vel reactivity diminished by adsorption with rabbit RBC stroma.

BACKGROUND: An anti-Vel, nearly missed in antibody identification studies, and the effect of a commercially available rabbit RBC stroma (RESt, Immucor) adsorptions on eight anti-Vel sera are reported. Anti-Vel is an antibody to an antigen of high prevalence. CASE REPORT: A 48-year-old woman with chronic vaginal bleeding presented with a Hct of 14.7 percent. The transfusion service was not informed of her history of anti-Vel when she was transferred from another institution. Studies performed on an emergency request for transfusion were interpreted as a cold autoantibody as adsorption with a c

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, m

Совпадение в полном тексте источника
… Cerebrosides Cerebrosides are a category of neutral glycosphingolipids that are mainly present in marine species. These compounds are extensively found in the brain and convert into ceramides, which are further transitioned into sphingomyelins, sulfatides, and other associated glycosphingolipids. … Name | Structure Fucoidan | Phlorotannins | Cerebrosides | Table 5 The below table lists compounds obtained from marine sources and their uses. …

What should rheumatologists know about Gaucher disease and Fabry disease? Connecting the dots for an overview.

Gaucher and Fabry diseases are lysosomal storage disorders in which deficient enzyme activity leads to pathological accumulation of sphingolipids. These diseases have a broad phenotypic presentation. Musculoskeletal symptoms and pain complaints are frequently reported by patients. Thus, rheumatologists can be contacted by these patients, contributing to the correct diagnosis, earlier indication of appropriate treatment and improvement of their prognosis. This review describes important concepts about Gaucher and Fabry diseases that rheumatologists should understand to improve patients' quality

Совпадение в полном тексте источника
… Based on their additional groups and complexity, sphingolipids are classified into sphingomyelins, cerebrosides, gangliosides, globosides, among others [ 8 , 12 , 13 ]. Complex sphingolipids are removed from plasma membranes and catabolized mainly through the lysosomal digestion system. …

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.

Совпадение в полном тексте источника
… Sphingolipid metabolism: fundamental biological functions Structure and classification of sphingolipids Sphingolipids are structurally divided into three main classes: sphingomyelin, cerebrosides (neutral glycosphingolipids), and gangliosides (acidic glycosphingolipids). … Simple forms with a single sugar are called cerebrosides (e. g., glucosylceramide platforms, GlcCer), while more complex forms with sialic acid residues are gangliosides ( McDonald and Davey, 2021 ). The structural diversity of sphingolipids directly dictates their functional specificity. …

CD200 является мощным новым фактором роста в Мультимиломе, зависящим от сигнала рецептора IGF1.

CD200 — это иммунный контрольно-пропускной пункт, безошибочно выраженный в 70% недавно диагностированных пациентов с множественной миеломой (ММ) и связанный с плохим исходом. Выражение CD200 клетками опухоли препятствует иммунной реакции через взаимодействие с CD200R и участвует в устойчивости к иммунной терапии. Однако его роль в опухоли остается слабой. В этом исследовании мы показываем, что клетки MM, перевыражающие CD200, представляют собой значительное пролиферативное преимущество в свободных культурных сыворотках, средних и клоногенных анализах. Преимущество роста клеток, опосредованное

Оптический анализ функционального воздействия демиелинации и ремиэлизации Cuprizone на межсферную нервную коммуникацию в антериорной кортекс через Corpus Callosum.

Cuprizone (CPZ) — широко используемый токсин, который вызывает демиелинизирующие заболевания в моделях животных, производя множественный склероз (MS), похожий на патологию в грызунах. CPZ является одним из немногих токсинов, которые вызывают демиелинацию и последующее воспоминание после прекращения ее применения. В этом исследовании рассматриваются функциональные последствия демиэлизации, вызванной КПЗ, и последующее восстановление нейронной связи в передней коре сингула (АКК) с уделением особого внимания соединению между полушариями через корпус каллосум (CC). Используя широкополосную высокос

Резюме ESPR 2013Европейское общество педиатрической радиологии 50th Ежегодное совещание и 36th Курсы для аспирантов. Июнь 3–7 2013. Будапешт, Венгрия.

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Глубинные пространственные омики MLADI-MS, управляемые квантовой каскадной лазерной микроскопией среднего инфракрасного изображения.

В пространственной "omics " высокоуверенные молекулярные идентификации необходимы для исследования сложной биологии и для пространственной биомаркировки. Однако нынешняя масс-спектрометрическая съемка (MSI) на основе пространственной "омики" должна скомпрометировать скорость получения данных и глубину биохимического профилирования. Здесь мы введём быструю, без этикеток квантовую каскадную лазерную микроскопию среднего инфракрасного изображения (QCL-MIR), чтобы направить MSI в высокоинтересные области тканей, такие маленькие, как гломерули почки, культурные многоклеточные сфероидные я