Regulation of the Induction and Function of Cytotoxic T Lymphocytes by Natural Killer T Cell

Cytotoxic T lymphocytes (CTLs) play a crucial role in the infections and the antitumor immunity. Induction and activation of antigen-specific CTLs is an important strategy in immunotherapy for various diseases, and several researchers have focused on the modulation of CTL induction and function. Natural killer T (NKT) cells are an important focus area of researchers studying immunomodulatory responses to tumors and infectious diseases. CD1d-restricted NKT cells consist of type I NKT cells and type II NKT cells. α-galactosylceramide (α-GalCer)-activated type I NKT cells secrete both Th1 (e.g., IFN-γ) and Th2 cytokines, affect the expression of costimulatory molecules in immune cells, and regulate the host immune system. Type II NKT cells, however, are stimulated by sulfatide, a self-glycolipid derived from myelin, and play an immunosuppressive role in animal model of autoimmune diseases. CTL generation, activation, and suppression are strongly affected by activated type I and type II NKT cells. Thus, the regulation of these NKT cells leads to the modification of CTL function. CTLs contribute to antimicrobial responses, antitumor immune and autoimmune responses. Understanding the role of NKT cells in the regulation of CTL generation, activation, and suppression enable the development of novel treatment strategies for these diseases

Expression of activin A in human keratinocytes at early stages of cultivation

AbstractActivins are members of the TGF-β superfamily and are classified into 3 types: activin A, which consists of a homodimer of βA, activin B, which consists of a homodimer of βB, and activin AB, which consists of a heterodimer of βAβB. We studied the expression of activin mRNAs by RT-PCR in normal human epidermis, cultured keratinocytes, and DJM-1 cells (a squamous cell carcinoma line). We could detect only activin A mRNA (βA) in normal human epidermis. In cultured keratinocyte and DJM-1 cells, activin βA mRNA was observed at 4 h but not at 96 h after plating. Activin A activity was detected in the conditioned medium of DJM-1 cells within 48 h. In addition, although follistatin mRNA was not observed in human epidermis in situ, it was transiently expressed in cultured cells at 4 h after plating. These findings suggest that the expression of these molecules in keratinocytes is associated with cell proliferation. In an in vitro tissue injury model, activin A was observed at the wound edge, where cell migration and proliferation may be activated. In DJM-1 cells cultured for 92 h, βA mRNA was observed 4 h after injury treatment. These findings suggest that activin A acts as a potent inducer of proliferation in vitro, at least in keratinocytes

Evidence of mature adipocyte proliferation regulated by proliferin

Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2′-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF

The shape of the emotion

　The emotion is an active reaction with being eloquent of the emotions such as the change of the look with the physiological reaction which is strong in the automatic nerves system, the immune system, the endocrine system which occurs with the organolepty which the creature felt.However, the definition of the emotion is ambiguous.　It is different roughly every learning field and for it, there is not a strict distinction of the emotion and the feelings.　The handling depends on the interval of the research area and the researcher.There seems to be possibility to complicate the discussion of the concerning with anxiety, theamygdala which is the nucleus of the fear and a cerebral limbic system for the ambiguousness of the definition and to make difficult.　Therefore, we made a chart with the emotion , feelings and the mood, placing as the differentreaction. In the tunnel of the tube-like of the comparatively gently long lasting mood, the feelings were wavering but supposed that doing of the eloquent of the emotion which is a physiological reaction and an active reaction didn\u27t accompany.　On the other hand, it supposed that an emotion was accompanied by the reaction which is physiological which is strong in the automatic nerves system, the immune system, the endocrine system and doing of the eloquent of the emotion physiological strong, deviating from the feeling control by the ventromedial prefrontal cortex.　Moreover, it considered about the relation, too, about the amygdala which is the existence like a nucleus of the experience like an emotion and the chronic pain

Sympathetic Block for Treating Primary Erythromelalgia

Primary erythromelalgia is a rare condition that's characterized by erythema, an increased skin temperature and burning pain in the extremities. The pain is often very severe, and treating erythromelalgia is frustrating and difficult. We report here on the case of a 12-year old girl with primary erythromelalgia in both lower extremities. The pain was refractory to medical treatment, but a bilateral sympathetic block with lidocaine and triamcinolone resulted in relief from the pain. Our experience with this disease demonstrates that sympathetic blocks are effective in improving the symptoms and they may be attempted on erythromelalgia patients who do not respond to other treatments, including medication and epidural blocks

Interferon-γ Decreases Ceramides with Long-Chain Fatty Acids: Possible Involvement in Atopic Dermatitis and Psoriasis

Ceramide (CER) with long-chain fatty acids (FAs) in the human stratum corneum (SC) is important for the skin barrier functions. Changes in the CER profile have been associated with abnormal permeability of dermatoses such as atopic dermatitis (AD) and psoriasis. In addition, interferon-γ (IFN-γ) has been known to be abundant in both AD and psoriatic skin lesions. In this study, we aimed to identify the mechanism underlying the alteration of FA chain length of CERs in these diseases. Mass spectrometry analysis of CERs in the SC showed that the proportion of CERs with long-chain FAs was significantly lower in AD and psoriasis patients than in healthy controls, and this reduction was more pronounced in psoriasis than in AD. Using cultured human keratinocytes and epidermal sheets, we found that only IFN-γ among various cytokines decreased the mRNA expression of elongase of long-chain fatty acids (ELOVL) and ceramide synthase (CerS), enzymes involved in FA chain elongation. Furthermore, quantitative analysis showed that IFN-γ decreased the levels of CERs with long-chain FAs. These results suggest that IFN-γ decreases CERs with long-chain FAs through the downregulation of ELOVL and CerS and that this mechanism may be involved in the CER profile alteration observed in psoriasis and AD

Sonographic Detection of Subcutaneous Foreign Bodies in 3 Cases

Subcutaneous masses caused by foreign bodies are frequently encountered in daily practice. Although the majority of foreign bodies such as metals can be detected by radiography, substances such as vegetative materials or wood are difficult to detect. To our knowledge, only a few studies have described the sonographic characteristics of foreign bodies. Herein, we report 3 cases where we studied the sonographic characteristics of the foreign bodies in the dermis and subcutaneous tissue. Our results revealed the following 3 foreign bodies: (1) glass, (2) vegetative material, and (3) a pencil core. Thus, sonographic examination is useful for the detection of foreign bodies

Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes

Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition to desmoglein-3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of cell-cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in cells treated with autoantibodies compared to those treated with normal antibodies. The apoptotic process induced by IgG autoantibodies was characterized by caspase-3 activation, Bcl-2 depletion and Bax expression. The present report demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes

The emerging role of FTY720 (Fingolimod) in cancer treatment

FTY720 (Fingolimod) is a clinically approved immunomodulating therapy for multiple sclerosis that sequesters T-cells to lymph nodes through functional antagonism of sphingosine-1-phosphate 1 receptor. FTY720 also demonstrates a proven efficacy in multiple in vitro and in vivo cancer models, suggesting a potential therapeutic role in cancer patients. A potential anticancer mechanism of FTY720 is through the inhibition of sphingosine kinase 1, a proto-oncogene with in vitro and clinical cancer association. In addition, FTY720's anticancer properties may be attributable to actions on several other molecular targets. This study focuses on reviewing the emerging evidence regarding the anticancer properties and molecular targets of FTY720. While the clinical transition of FTY720 is currently limited by its immune suppression effects, studies aiming at FTY720 delivery and release together with identifying its key synergetic combinations and relevant patient subsets may lead to its rapid introduction into the clinic

Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

<p>Abstract</p> <p>Background</p> <p>Drug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug). We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug) interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases.</p> <p>Case presentation</p> <p>We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6) DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS) was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die) that was tapered very slowly. The patient recovered completely.</p> <p>Conclusions</p> <p>The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration) and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.</p