M1 and M2 Myeloid Cells in Inflammation

Inflammation is triggered in the innate immune response by tissue myeloid cells, macrophages in peripheral tissue and microglia in the nervous system, in response to microbial or endogenous danger signals.

The plasticity of these cells developing into pro-inflammatory M1 and anti-inflammatory M2 phenotypes is remarkable. Polarization of macrophages depends on local environmental factors, especially cytokines and growth factors.

Interferon-γ (IFN-γ) and bacterial lipopolysaccharide together polarize macrophage into the M1 phenotype which produces reactive oxygen species, nitric oxide, and inflammatory cytokines such as tumor necrosis factor-α. However, NO appears to play a negative role in M1 macrophage differentiation.

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The Expanding List of Redox-Sensing Transcription Factors in Mammalian Cells

Mammalian cells do not survive in the absence of redox reactions; oxidation and reduction predominate in the swamp of metabolic biochemical reactions inside the cell. In a situation which is less stoichiometric, subtle alterations of the redox status in the intracellular environment also have significant impacts on cell biology. Changes in the intracellular redox status can be assessed by quantifying the reduction potentials of various intracellular redox couples.

However, in practice, the motto “redox environment” used by cell biologists usually means the relative abundance of reactive oxygen species (ROS) inside or in proximity of a cell. More than three decades ago people have observed that mammalian cells can actively produce ROS, and utilize these molecules to regulate cell functions.

Then it has been discovered that in prokaryotes, some transcription factors switch on and off their DNA binding activity by directly sensing the presence of per oxidant ROS molecules such as superoxide and hydrogen peroxide, which regulate gene expressions. This phenomenon was also observed in mammalian cells.

Paranasal Sinus Lymphoma Presenting as an Orbital Mass

The paranasal sinuses are rare sites for origination of primary Non-Hodgkin’s lymphoma (NHL). Most often, primary paranasal lymphomas are diffuse large B-cell lymphomas (DLBCL) associated with a poor prognosis. This paper describes an uncommon case of ethmoid sinus lymphoma with lateral displacement of the left orbit and involvement of the nasal vault, skull base, and frontal sinuses.

Excisional biopsy and flow cytometry findings favored the diagnosis of DLBCL, non-germinal center type. Moreover, CT showed an epigastric mass and enlarged lymph nodes along the left iliac chain and spleen. Radiation therapy was immediately started and the patient achieved significant symptomatic relief after four treatments.

Accurate diagnosis of extranodal NHL lymphomas through a thorough history, physical exam, imaging, and immunopathology is necessary to initiate prompt treatment of this rare, aggressive disease.

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Subtleties and Dynamics of Antibody Function

Antibody, nature’s most magnificent molecule, has come of age moving forward from an era of polyclonal and monoclonal antibodies to its applications as functional antibody fragments or modifications thereof for developing new drugs against vexing diseases, such as, cancer and viral infections.

The conventional therapies against these diseases have not been successful resulting in a shift towards development of novel antibody-based therapeutics. The clinical success of antibodies can be assessed from their major commercial impact as evidenced by the market for antibody drugs being over $60 billion in 2013, which is expected to double globally within the decade.

Current knowledge of the structure and function of bovine antibodies provides important clues to strategically design antibody-based drugs by optimized engineering.

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Multiple Defects Impair the HLA Class II Antigen Presentation Capacity of Burkitt Lymphoma

Burkitt lymphoma (BL) is a B-cell malignancy which occurs with varying clinical manifestations and frequencies. The most well-known presentation of BL is found in areas which are holoendemic or hyperendemic for malaria. This endemic BL occurs primarily in children and presents as tumors of the jaw.

Though a strong association exists between endemic BL and malaria, the nature of the relationship remains unclear. A sporadic form of BL also occurs elsewhere in the world and typically causes tumors in the gut and upper respiratory tract.

There are various other contributing factors which may lead to development of BL, including Epstein-Barr Virus (EBV) and Human Immunodeficiency Virus (HIV). EBV has long been associated with development of BL and is found in nearly all cases of endemic BL but, in spite of intense research, the relationship between EBV and BL remains unclear. It is generally believed that infection with EBV somehow drives transformation which then leads to development of BL

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The Trouble with HARRIS

In an old movie, “The trouble with Harry” (Paramount Pictures, 1955), a little masterpiece of black comedy directed by a great Alfred Hitchcock at his best, the inhabitants of a small village in Vermont have to manage the dead body of a man, named Harry, found on a hillside.

Three of the main characters in the movie each believe that he or she is the person who killed Harry incidentally and everybody tries to hide Harry’s corpse, who becomes literally a “walking dead”, hauled and hidden, far away from the local policeman attention, for all the movie along. So, all the main characters have to bury the body and then dig it up again several times for different reasons, until the village’s doctor establishes at last, that Harry died of natural causes.

Actually, drug allergy and drug hypersensitivity are treated by most of the doctors as Harry’s dead body: they try to hide or to minimize the onset of an allergic reaction to a drug they have prescribed or administered.

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The Role of Microparticles in Rheumatic Diseases and their Potentials as Therapeutic Tools

Microparticles (MPs, also known as microvesicules or ectosomes) are heterogeneous subcellular vesicular particles (0.1-1.0 m in diameter) released constitutively from cells and platelets undergoing cell activation or cell death by blebbing or shedding. Platelet MPs are usually the most abundant type in blood.

The presence of basal levels of MPs is common in healthy individuals, and is estimated, in peripheral blood, to range between 5 and 50 g/ml (105-106 MPs/ml). Numerous types of MPs have been characterized with important physiologic effects by the detection of different cell surface antigens reflecting their origin and activation method.

MPs represent distinct subcellular structures and serve a prominent role in homeostasis and intercellular communication including immune activation. They can transfer bioactive molecules from parental to target cells, allowing for regulation and amplification of several biological mechanisms such as activation, apoptosis, coagulation, and proliferation.

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IMMUNOTHERAPY IN PANCREATIC CANCER; THE ROAD LESS TRAVELED

Pancreatic cancer shows extremely low responses to chemo- and radiation therapies due to its inherent genetic instability, immunosuppressive microenvironment, and the complex peritumoral stroma.

They make the pancreatic cancer most lethal malignancy with 5 year survival of less than 6%, so the need of new therapeutic approaches is urgently demanded. Immunotherapies have shown promises in other multiple cancers by augmenting anti-tumor immunity, so it stood out for the alternative care of pancreatic cancer.

However, up to now, immunotherapeutic agents lack efficacy in pancreatic cancer. In this review, we give an overview of immune-related therapeutic strategies, clinical trials in pancreatic cancer and current obstacles that we face. We discuss the ways to overcome those current obstacles here, and by getting over them, we hope to get over the poor prognosis of pancreatic cancer.

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Alzheimers Disease of the Immune System: A New Variant of Immune Deficiency

The interaction between infectious pathogens and the immune system has been a focus of research for many years. However, the failure of re-recognition or immune memory of infectious pathogen remains a clear mystery A memory B cell defect coupled with low levels of C1-INH and/or C1-INH function-failure of both the innate and adaptive immune components-may lead to persistent unresolved infection.

Here we present 3 case studies that explore the abnormal immune response that may lead to persistent infection. These cases offer possible clarification of a longstanding clinical observation that some patients may develop a post infectious syndrome that includes various neurological symptoms and unusual fatigue.

These patients may have positive serology seen only during acute infectious phase and have a documented positive PCR, suggesting active presence of the pathogen. The unusual presentation is prolonged and irreversible.

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Recurrent Wheezing in Infants and Young Children and Bronchial Hyper- Responsiveness

Childhood wheeze is a common phenomenon, and has seasonal prominence, largely focused on a viral respiratory syncytial infection (RSV). When children wheeze again, or repeatedly, and a RSV infection was previously documented, a ready explanation is available.

Recent data strongly supports the likelihood of rhinovirus as the agent for the next sequence wheeze, and with the recurrent wheeze a risk for asthma development. Without a RSV vaccination this postbronchiolitis wheezer will fit the profile offered in the original review.

There remains however, as mentioned in 2003, a concern these postbronchiolitis wheezers can morph into asthma, and a recent study suggest a genetic association. This “phenotype” was more recently discussed, but termed “severe intermittent wheeze”. Atopic features and eventual asthma, however was not uncommon in the phenotype discussed. It seems the medical community in 2016 still struggles with the post-RSV phenotype.

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Basal Serum Cortisol and Adrenocorticotropic Hormone Levels in Patients with Atopic Dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with eczematous pruritic lesions. Topical corticosteroids are the most widely used and the mainstay of treatment for AD. There are some studies that percutaneous systemic absorption of topical steroids may occur and lead to suppression of hypothalamic-pituitaryadrenal axis (HPAA).

However, almost in all of these studies, “basic” HPAA function (before application of topical steroids) was not evaluated. The aim of this study was to investigate basal serum cortisol, adrenocorticotropic hormone (ACTH), and IgE levels in patients with AD and their correlation with disease severity.

Levels of basal serum cortisol, ACTH, and IgE were assessed by ELISA in 31 patients with AD and 31 control subjects. Clinical severity of AD was evaluated by the SCORAD (SCORing Atopic Dermatitis) index. Results: Data analysis showed no statistical difference for basal serum cortisol and ACTH levels between two groups.

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Alexithymia in Systemic Lupus Erythematosus: A Tight Relation with Mood States

The difficulty in identifying, differentiating and expressing emotions is a neuropsychological condition called alexithymia. During the last years it has grown the interest of scientific community for alexithymia, in particular in2 chronic conditions.

Crescent literature data demonstrated that a considerable number of SLE patients present difficulty not only in identifying, differentiating, and articulating emotions but also in differentiating them from bodily sensations, configuring the alexithymia complaint.

Alexithymia seems to be not related to SLE disease activity but tightly related to mood states. Identify proper pharmacological and psychological approach to alexithymia in SLE patients is a major challenge for future research.

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Epitope Driven Broad Spectrum Peptide Vaccines against MDR Pathogens

Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumonia have evolved as a group of co-existing multidrug resistant nosocomial pathogens spreading worldwide.

Overuse of antibiotics has led to the emergence of pan drug resistant bacterial strains and has made all antimicrobial agents superfluous including carbapenems and even the last resort antibiotic-colistin, resulting in high mortality rates among the hospitalized patients.

Vaccination is highly effective and successfully used strategy that reduces the incidence of infectious diseases, yet efforts towards development of vaccines for nosocomial infections are scant. In this direction, a broad spectrum vaccine is the futuristic need providing protection not only against A. baumannii but against the whole group of co-existing nosocomial pathogens.

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