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Immune System Diseases - Top 30 Publications

Apoptotic Endonuclease EndoG Inhibits Telomerase Activity and Induces Malignant Transformation of Human CD4+ T Cells.

Telomerase activity is regulated by an alternative splicing of mRNA of the telomerase catalytic subunit hTERT (human telomerase reverse transcriptase). Increased expression of the inactive spliced hTERT results in inhibition of telomerase activity. Little is known about the mechanism of hTERT mRNA alternative splicing. This study was aimed at determining the effect of an apoptotic endonuclease G (EndoG) on alternative splicing of hTERT and telomerase activity in CD4+ human T lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of the active full-length hTERT variant and upregulated the inactive alternatively spliced variant. Reduction of full-length hTERT levels caused downregulation of the telomerase activity, critical telomere shortening during cell division that converted cells into the replicative senescence state, activation of apoptosis, and finally cell death. Some cells survive and undergo a malignant transformation. Transformed cells feature increased telomerase activity and proliferative potential compared to the original CD4+ T cells. These cells have phenotype of T lymphoblastic leukemia cells and can form tumors and cause death in experimental mice.

Extracellular Actin in Health and Disease.

This review considers the functions of extracellular actin - cell surface bound, associated with extracellular matrix, or freely circulating. The role of this protein in different pathological processes is analyzed: its toxic effects and involvement in autoimmune diseases as an autoantigen. The extracellular actin clearance system and its role in protection against the negative effects of actin are characterized. Levels of free-circulating actin, anti-actin immunoglobulins, and components of the actin clearance system as prognostic biomarkers for different diseases are reviewed. Experimental approaches to protection against excessive amounts of free-circulating F-actin are discussed.

Multiple Myeloma: Diagnosis and Treatment.

Multiple myeloma accounts for 1.6% of all cancer cases and approximately 10% of hematologic malignancies in the United States. In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths. Patients older than 65 years account for 85% of those diagnosed with multiple myeloma, and there is a twofold increased incidence in blacks compared with whites. Patients may present with bone pain or with symptoms that are often nonspecific, such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss. Many patients present with only laboratory abnormalities, such as anemia, renal disease, and elevated protein levels. The diagnosis of multiple myeloma requires increased numbers of immature, abnormal, or atypical plasma cells in the bone marrow; a monoclonal protein in the serum or urine; or characteristic bone lesions. The diagnostic workup in a patient with suspected multiple myeloma should include a complete blood count with differential; serum chemistries; creatinine, lactate dehydrogenase, and beta2-microglobulin tests; immunoglobulin studies; skeletal survey; and bone marrow evaluation. Initiation of chemotherapy and assessment of eligibility for autologous stem cell transplantation require referral to an oncologist. Most patients with multiple myeloma will receive thromboprophylaxis, bisphosphonate therapy, and prophylaxis against infection at some point in their treatment. Family physicians play a role in assessing these patients for infection, adverse treatment effects, and renal and thrombotic complications, and in managing issues related to pain, nutrition, and psychosocial support.

Primary central nervous system lymphoma: essential points in diagnosis and management.

Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma. PCNSL is defined as lymphoma involving the brain, leptomeninges, eyes, or spinal cord without evidence of lymphoma outside the CNS. Treatment includes induction with chemotherapy and consolidation with whole-brain radiotherapy or high-dose chemotherapy supported by autologous stem cell transplantation. High-dose methotrexate is the most important drug in cases with PCNSL, and this drug will be used in combination with small molecules, BTK inhibitors, new monoclonal antibodies, and checkpoint blockers.

Chrysin as an Anti-Cancer Agent Exerts Selective Toxicity by Directly Inhibiting Mitochondrial Complex II and V in CLL B-lymphocytes.

We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria. Our findings may provide a potential therapeutic approach for using chrysin to target mitochondria in CLL B-lymphocytes.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Presentation of calcinosis cutis universalis in mixed connective tissue disorder: an encounter during hip arthroplasty.

A woman aged 23 years with a diagnosis of mixed connective tissue disorder presented with left groin pain extending over 6 months. Workup revealed avascular necrosis of the femoral head (Grade 3) secondary to systemic lupus erythematosus and chronic steroid intake. An uncemented total hip arthroplasty was considered as the patient was only in the third decade of life. During the preop workup, careful clinical assessment had revealed multiple subcutaneous nodules affecting the extensor musculature limited to the gluteal region, anterior and posterior aspects of the thigh. The diagnosis of calcinosis cutis universalis was made after a CT revealed calcified nodules in the subcutaneous, subfascial and muscular planes. A total hip arthroplasty using the posterior approach was performed with minimal trauma to the calcified nodules and thereby preventing a source of persistent drainage and reducing morbidity due to infection.

Trends in Sero-Epidemiology of Human Immunodeficiency Virus in Voluntary Blood Donations in Iran, 2008-2013.

Various strategies are implemented to increase blood safety. However, there is always a small amount of residual risk. The amount of risk is associated with the incidence and prevalence of infection in the community. Since increases in the prevalence and changing the pattern of HIV transmission have been observed in the community, monitoring of HIV prevalence among general population and blood donors is necessary. This study aimed to determine the prevalence of HIV in Iranian blood donations. Demographic status and donation type were also investigated in HIV positive blood donors.

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis.

Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14(bright)CD16(-) monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.

Guillain-Barré Syndrome Presenting with Sinus Node Dysfunction and Refractory Shock.

BACKGROUND Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy that is usually associated with preceding respiratory or gastrointestinal infection and has the hallmark manifestation of ascending flaccid paralysis. We report an atypical presentation of GBS. CASE REPORT A 76-year-old male presented with acute onset of diaphoresis and altered mental status. He subsequently developed severe bradycardia and refractory hypotension, which initially responded to dopamine infusion. A temporary pacemaker wire was placed to stabilize the heart rate but hypotension persisted. Acute autonomic dysfunction was suspected. Head and chest imaging was unrevealing. Lumbar puncture revealed albuminocytologic dissociation that was consistent with a diagnosis of GBS. Hospital course was complicated with acute kidney injury and metabolic acidosis. Plasmapharesis was initiated. The patient eventually died of multi-organ failure. CONCLUSIONS Autonomic dysfunction is a known but rare presentation of GBS. In patients presenting with refractory bradycardia and hypotension, GBS should be considered in the differential diagnosis.

The varieties of psychosis in multiple sclerosis: A systematic review of cases.

Multiple Sclerosis (MS) is known to be associated with a wide range of psychiatric symptoms, particularly with affective disorders. However, a link to psychotic disorders has not been fully established.

Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab.

Several disease-modifying drugs (DMD) are available for the treatment of MS, and most patients with relapsing-remitting disease are currently treated. Data on when and how DMD treatment can be safely discontinued are scarce.

Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses.

Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials.

Access, delivery and perceived efficacy of physiotherapy and use of complementary and alternative therapies by people with progressive multiple sclerosis in the United Kingdom: An online survey.

All people with progressive MS in the United Kingdom should have access to physiotherapy through the National Health Service (NHS). However levels of access and delivery are unknown. Furthermore there is no research on perceived efficacy of physiotherapy or the use of complementary and alternative medicine in people with progressive MS in the United Kingdom.

Classifying PML risk with disease modifying therapies.

To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS).

Higher prevalence of restless legs syndrome/Willis-Ekbom disease in multiple sclerosis patients is related to spinal cord lesions.

Multiple sclerosis (MS) is connected with higher prevalence of secondary restless legs syndrome/Willis-Ekbom disease (RLS/WED). Aim of this study was to determine risk factor for developing symptoms of RLS in MS patients.

Sexual dysfunction levels in iranian women suffering from multiple sclerosis.

Sexual dysfunction (SD) is a common complaint in women who suffer from Multiple Sclerosis (MS), which has been categorized in three levels (primary, secondary, and tertiary) in previous studies. This study was conducted to assess the prevalence of sexual dysfunction (SD) at each level, and to identify associated factors and their impacts on SD in married women who suffer from Multiple Sclerosis. This study was conducted in Iran where the cultural barriers are recognized as important challenges in sexual function.

Vogt Koyanagi Harada Syndrome mimicking multiple sclerosis: A case report and review of the literature.

Vogt Koyanagi Harada (VKH) Syndrome, also called uveomeningioencephalitis, is a chronic disorder characterized by inflammation of the uvea, meninges, auditory system, and integumentary system. The association between VKH syndrome and multiple sclerosis (MS) has been reported only once in the literature in a patient who developed VKH syndrome after two years of the diagnosis of MS. In this article, we report a case who was misdiagnosed and treated as MS until she was proven to have VKH syndrome, and a diagnosis of MS was excluded. VKH syndrome is a systemic disorder that may present with clinical and/or radiological features mimicking MS. Applying diagnostic criteria is extremely important for confirming or excluding the diagnosis. Detailed history and physical examination are of paramount importance to score the final diagnosis. Rigorous search for red flags for both conditions is very helpful.

Perinatal characteristics and obstetric complications in mothers with multiple sclerosis: Record-linkage study.

Multiple sclerosis (MS) predominantly onsets in women of reproductive age. The possibility of adverse obstetric and perinatal outcomes is a likely source of concern to pregnant women with MS and their clinicians. We aimed to compare the characteristics of the pregnancies of mothers with or without MS.

Comparing epidemiology and baseline characteristic of multiple sclerosis and neuromyelitis optica: A case-control study.

Autoimmune syndromes such as Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) are chronic, demyelinating diseases of the central nervous system which usually affect young adults. Both environmental risk factors and genetic susceptibility have been proposed to explain the etiology of these diseases. The aim of this study was to compare epidemiology and possible risk factors in MS and NMO in Tehran, Iran.

There is less MRI brain lesions and no characteristic MRI Brain findings in IIDDs patients with positive AQP4 serology among Malaysians.

The recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs.

The association between physical activity and sleep characteristics in people with multiple sclerosis.

The majority of individuals with multiple sclerosis (MS) suffer from sleep disorders. In this study, we investigated the relationship between physical activity and sleep characteristics in MS patients.

Sex differences in outcomes of disease-modifying treatments for multiple sclerosis: A systematic review.

Multiple sclerosis (MS) is a chronic immune mediated demyelinating disease of the central nervous system that exhibits sexual dimorphism and may benefit from sex-specific treatment. To investigate a potential influence of sex on immunomodulatory therapeutic effects in patients with MS, we performed a comprehensive analysis of published studies examining sex differences in the effects of disease-modifying treatments (DMTs) for MS.

Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterised by psychiatric symptoms, movement disorder and seizures often evolving into a severe encephalopathy. An overlap has recently been recognised between anti-NMDAR encephalitis and inflammatory demyelinating disorders, particularly neuromyelitis optical spectrum disorder (NMOSD). In this case report, we describe two patients with an initial presentation consistent with anti-NMDAR encephalitis who have subsequently developed relapsing-remitting multiple sclerosis (MS) and discuss the literature pertaining to potential overlap between NMDAR encephalitis and inflammatory demyelinating disorders.

Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis.

Visual evoked potentials and spectral-domain optical coherence tomography are common ancillary studies that assess the visual pathways from a functional and structural aspect, respectively.

MicroRNA-155 Downregulation Promotes Cell Cycle Arrest and Apoptosis in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients' tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.

Headache in Neuromyelitis Optica.

Neuromyelitis optica (NMO) classically features a clinical presentation that includes longitudinally extensive transverse myelitis and optic neuritis. However, many other pathognomonic phenomena have more recently been described in patients diagnosed with NMO, including intractable hiccups, vomiting, and painful tonic spasms, but less has been reported regarding the relationship between NMO and headache. Though headache is well established as both a symptom and comorbidity of multiple sclerosis (MS), it has been much less described thus far in the NMO literature and warrants more careful evaluation. Many questions remain unanswered about the relationship between NMO and headache, including headache prevalence in certain groups, distribution of primary and symptomatic headache disorders that are seen most frequently and the specific neuroimaging findings that are associated with an increased risk of headache.

Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.

Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies.

IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population.

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.