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Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow.

Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morp … otype+,CD19+,CD20+, PCA-1-,cytoplasmic-idiotype- lymphocytes, to CD19-,PCA-1+,cytoplasmic-idiotype+ plasma cells that are surface-idiotype- or weakly surface-idiotype+. In one patient, some of the tumor cells co-expressed surface idiotype and CD10. The tumor B lymphocytes were activated in vitro to synthesize paraprotein by pokeweed mitogen (PWM), and by low m …

Angiomatosis retinae. An ultrastructural study and lipid analysis.

A nonfamilial case of agiomatosis retinae (retinal hemangioblastoma) was studied by electron microscopy. In addition to the three major types of cells previously identified within the tumor (endothelial cells, pericytes, heavily lipidized stromal cells), fibrous astrocytes in different stages of lipidization were also found. The endothelial cells were fenestrated, providing the basis for the extravasated exudate that is characteristic of the tumor. The pericytes were completely surrounded by casement membranes and displayed no significant lipidization; in a cellular plaque of vasular tissue at

B cell-specific mAb-siRNA conjugates improve experimental myasthenia.

Myasthenia gravis (MG) is a debilitating autoimmune disease characterized by muscle fatigue and weakness caused by autoantibody- and complem … D268 (B cell-activating factor receptor) in mature B cells and CD269 (B-cell maturation antigen) in plasma cells concomitantly with reducing the levels of acetylcholine receptor (AChR)-specific autoantibodies. PEGylation, but not pretreatment with an antibody against type 1 interferon receptor, further improved duoconjugate-induced reduction in the autoantibod …

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma.

Inositol polyphosphate-4-phosphatase type II (INPP4B) has been identified as a tumor suppressor, while little is known about its expression and function in multiple myeloma (MM). In this study, we evaluated the expression of INPP4B in 28 cases of newly diagnosed MM patients and 42 cases of extramedullary plasmacytoma (EMP) patients compared with normal plasma cells and found that low INPP4B expression was correlated with poor outcomes in MM patients. Moreover, expression of INPP4B in seven MM cell lines was all lower than that in normal plasma cells. In addition, loss of function of INPP4B pro…

Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.

The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos

IL-10 critically modulates B cell responsiveness in Rankl-/- mice.

The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl(-/-) mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells ass…

HMG-CoA reductase inhibitor simvastatin overcomes bortezomib-induced apoptosis resistance by disrupting a geranylgeranyl pyrophosphate-dependent survival pathway.

Simvastatin is a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway required for the biosynthesis of cholesterol and higher isoprenoids such as geranylgeranyl pyrophosphate (GGPP). Apart from its capacity to lower cholesterol plasma levels and to protect against cardiovascular disease, simvastatin induces apoptosis in various cancer cells. We have generated human Namalwa Burkitt lymphoma cells that display general apoptosis resistance and hyperproliferation due to increased expression and proteolytic activity of 26S proteasomes in response to continu

Coexistence of hyperplasia of renomedullary interstitial cells and juxtaglomerular cells after acute occlusion of renal artery.

A left renal artery aneurysm was found in a 45-year-old normotensive man. In an attempt to evade the possible occurrence of aneurysmal rupture, aneurysmectomy in addition to left renal biopsy (first surgery) was performed. This vascular operation led to a virtually complete renal artery stenosis concomitant with the development of hypertension. The renin-angiotensin-aldosterone system and levels of plasma prostaglandins were also increased following this failed surgery. Reconstruction of the affected renal artery was technically so difficult that left nephrectomy was carried out (second surger

One-carbon metabolism upregulated in lupus promotes the differentiation and effector functions of human B and T cells.

OBJECTIVES: SLE is a multi-organ inflammatory disease driven by autoreactive B and T cells. The serine, glycine and one‑carbon (SGOC) network controls the proliferation and effector functions of mouse B and T cells; however, its roles in human lymphocytes and SLE are largely unknown. We hypothesize that this network is upregulated in SLE and regulates the functions of human B and T cells. METHODS: We employed RT-qPCR and single-cell RNA-seq to analyse SGOC expression in B and T cells from SLE patients and healthy controls. The proliferation of human B and T cells, plasma cell differentiation,

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail.

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. F

MAGa: Monoclonal Autoimmune Gammopathies.

There is a growing recognition of bidirectional relationships between immune phenomena in plasma cell disorders, such as multiple myeloma and its precursor malignancies, including autoimmune phenomena that either precede or complicate the development of neoplasms. The development of specific autoimmune disorders is a well-known aspect of B-cell lymphoproliferative diseases. At the same time, the development of plasma cell dyscrasia in patients with autoimmune diseases is well established. This may suggest that some subclones of multiple myeloma and its precursor, monoclonal gammopathy of undet

Функциональное иммунное профилирование переводит динамику Т-клеток в прогнозируемые биомаркеры для иммунотерапии миеломы.

Биспектифические Т-клеточные энджеры (TCE), мишенирующие к BCMA или GPRC5D, улучшили исходы у пациентов с резидуальным/рефракторным множественным миеломой (ММ), однако до 40% пациентов являются первичными рефракторными, и предиктивные биомаркеры крайне ограничены. Чтобы решить эту неудовлетворенную клиническую потребность, мы разработали изображение-ориентированную высокопроизводительную эквивалентную вне организма пробу, используя мононуклеаты костного мозга, полученные от пациентов, подвергнутые воздействию теclistamаба или талкетамаба. Мультиплексная иммунофлуоресценция позволила количестве

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… NR samples showed neither plasma cell lysis nor T cell expansion. In contrast, CT/EX samples demonstrated marked plasma cell lysis and robust T cell expansion. CT samples exhibited significant plasma cell lysis without accompanying T cell expansion (Fig. 1C–F ). … Fig. 5 Target gene loss impairs plasma cell lysis and T cell expansion. A Correlations of CD138-DRS and CD3-DRS with the fraction of BCMA⁺ plasma cells (TEC; left) and GPRC5D⁺ plasma cells (TAL; right); n = 35 (TEC) and n = 32 (TAL) patient samples with flow cytometry data. …

Evaluating plasma extracellular vesicle microRNAs as possible biomarkers for osteoarthritis.

OBJECTIVE: MicroRNAs (miRNAs) are being launched as biomarkers for various diseases, but a robust biomarker for articular cartilage pathology has yet to be discovered. Here we evaluate plasma extracellular vesicle (EV) miRNAs as possible biomarkers for osteoarthritis (OA). METHOD: We compared miRNA levels found in plasma EVs from patients with OA with controls without OA using next generation sequencing (NGS) technique. The patient and control pairs were matched for age, gender and body mass index. RESULTS: 23 pairs of patients and controls were included. Patients with OA differed significan

Mechanism of morphine in increasing plasma cyclic GMP level in male mice.

Morphine given systemically or centrally increases the plasma concentration of cyclic GMP in male, ddY strain mice. Normorphine also increased the plasma cyclic GMP level, whereas the same dose of ketocyclazocine and SKF 10,047 had no effect. The effect of morphine on plasma cyclic GMP was mimicked by opioid peptides such as (D-Ala2, Met)-enkephalinamide, FK 33,824 or beta-endorphin. The effect of morphine and opioid peptides on plasma cyclic GMP was antagonized by naloxone, indicating the involvement of the opiate receptor. The increase in plasma cyclic GMP elicited by morphine was abolished

Effect of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) in a mouse model of atopic dermatitis.

The effects of exposure to clothianidin (CLO), a neonicotinoid pesticide (NN), on the thymus and intestinal microbiota were recently revealed. Immune cells express nicotinic acetylcholine receptors (nAChRs), an NN target, suggesting CLO may disrupt the immune system. However, the relationship between CLO and atopic dermatitis (AD) is unknown. We administered a no-adverse-effect-level (NOAEL) dose of CLO to male NC/Nga mice with induced AD and measured, at three time points, key AD symptom indicators: epidermal thickening, mast cell number, total plasma IgE, and histamine levels. CLO increased

Cutaneous involvement as initial presentation of multicentric plasmacytic Castleman disease.

Castleman disease (CD) is an unusual lymphoproliferative disorder characterized by multiple lymphadenopathy accompanied by marked systemic inflammatory symptoms. CD can be unicentric (UCD) or multicentric (MCD), and it can be classified into three types based on histopathology: hyaline vascular type, plasma cell type, and mixed hyaline vascular and plasma cell type. CD involving skin is an unusual clinical manifestation. Abnormalities including rash, hyperpigmentation, cherry hemangiomatosis, paraneoplastic pemphigus, and Kaposi sarcoma have been reported to occur in MCD. Here, we reported an

Pseudo-monoclonal gammopathy due to autoimmune disease: a case report.

Hyperglobulinemia is a common manifestation of plasma cell disease, and it is sometimes caused by autoimmune diseases (AIDs). We report an uncommon presentation of hyperglobulinemia, with a high amount of plasma cells in bone marrow, pancytopenia, hematemesis, and splenomegaly in an 18-year-old woman. Some examinations were performed to determine the diagnosis, including serum protein electrophoresis, immunofixation electrophoresis, the free light chain assay, abdominal enhanced computed tomography (CT) and CT venography, and positron-emission tomography-CT. The patient was finally diagnosed w…

Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel.

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radi…

[Clinical study of inflammatory diseases, which are difficult to differentiate from tumorous lesions].

Fourteen inflammatory disease cases in which differential diagnoses from tumorous lesions had been difficult and which were confirmed by thoracotomies, were studied. They included 4 plasma cell granulomas, 3 pulmonary abscesses, 2 fungal diseases, and one case of pseudolymphoma, lymphocytic interstitial pneumonia, Wegener's granulomatosis, round atelectasis, organized pneumonia, respectively. In some cases with plasma cell granuloma, lymphoproliferative disease, Wegener's granulomatosis and round atelectasis, it might be possible to correctly diagnose the cases preoperatively, on chest X-ray,

Lacaziosis: immunohistochemical evaluation of elements of the humoral response in cutaneous lesions.

Lacaziosis is a cutaneous mycosis caused by the fungus Lacazia loboi, described in different countries of Latin America and prevalent in the Amazon region. The ineffective immune response against the agent seems to be related to a Th2 pattern of cytokines. There are few reports exploring elements of the humoral response in these lesions. Our aim was to investigate some elements focusing on B cells, plasma cells and local expression of IgG and IgM antibodies. Forty skin biopsies of lower limbs were selected. The diagnosis of lacaziosis was based on direct mycological examination and histologica…