A combination of immunological reaction to a drug and HHV-6 reactivation results in the severe course of DIHS. The demonstration of HHV-6 reactivation is a useful marker of diagnosis as well as prognosis in DIHS.
Immunotherapy (IT) has become an accepted therapeutic modality. We previously reported that intracellular hyperthermia (IH) using magnetic nanoparticles induces antitumor immunity. We undertook these studies in order to study the combined effects of IT and IH on melanoma. Magnetite cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs were injected into a B16 melanoma nodule in C57BL/6 mice, which were subjected to AMF for 30 min. The temperature at the tumor reached 43°C and was maintained by controlling the magnetic field intensity. At 24 h after IH, interleukin-2 (IL-2) or granulocyte macrophage-colony stimulating factor (GM-CSF) was injected directly into the melanoma. Mice were divided into six groups: group I (control), group II (IH), group III (IL-2), group IV (GM-CSF), group V (IH + + + +IL-2), and group VI (IH + + + +GM-CSF). yperthermia has been used for many years to treat a wide variety of tumors both in experimental animals and patients.1) The most commonly used heating method in clinical settings is capacitive heating using a radiofrequency (RF) electric field.2) However, specifically heating tumors by capacitive heating using an RF electric field is difficult, because the heating characteristics are influenced by various factors, such as tumor size, position of electrodes, and adhesion of electrodes at uneven sites. From a clinical point of view, a simple heat mediator is preferable for superficially seated tumors such as cutaneous melanoma. Magnetic nanoparticles have been applied to generate hyperthermia in an attempt to overcome these disadvantages.3, 4) These magnetic nanoparticles generate heat in an alternating magnetic field (AMF) due to hysteresis loss.
5)We have developed "magnetite cationic liposomes" (MCLs) for intracellular hyperthermia (IH).6, 7) MCLs were developed to show improved adsorption and accumulation in tumor cells and have a ten-fold higher affinity for tumor cells than for neutrally charged magnetoliposomes due to electrostatic interaction with the negatively charged cell membrane.6) In our in vitro experiments, 55% of MCLs were incorporated into cells and the intracellular magnetic nanoparticles could generate heat under AMF.6) We have also demonstrated the efficacy of IH using MCLs against T-9 rat glioma in an in vivo study.
8)We previously reported that our IH system induced antitumor immunity. 9) Hyperthermia is known to induce heat shock proteins (HSPs).10) Because expression of HSP70 protects cells from heat-induced apoptosis, 11) HSP70 expression has been considered to be a complicating factor in hyperthermia. On the other hand, recent reports have shown the importance of HSPs, such as HSP70, HSP90 and glucose-regulated protein 96, in immune reactions.12, 13) HSP-mediated antitumor immunity was reported to cause a vaccine effect due to HSP-peptide complexes purified from human melanoma cells.14) With regard to the mechanism of antitumor immunity induced by IH, we demonstrated th...
Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant inheritance. We have clarified for the first time four pathological mutations of the double-stranded RNA-specific adenosine deaminase gene (ADAR1 or DSRAD) in four DSH pedigrees. In this paper, we report 16 novel mutations containing six missense substitutions (p.V906F, p.K1003R, p.G1007R, p.C1036S, p.S1064F, p.R1078C), two splice site mutations (IVS2+2T>G, IVS8+2T>A), six frameshift mutations (p.H216fs, p.K433fs, p.G507fs, p.P727fs, p.V955fs, p.K1201fs), and two nonsense mutations (p.R426X, p.Q600X) found in Japanese patients with DSH. We did not establish any clear correlation between the clinical phenotypes and the genotypes of ADAR1 gene mutations in our examination of 16 cases plus four pedigrees. None of the different mutations identified in our studies of 20 cases suggested any founder effect. Furthermore, we did not identify any mutations in the ADAR1 gene of three patients with dyschromatosis universalis hereditaria or three patients with acropigmentatio reticularis, indicating that the two diseases are completely different from DSH, although they have sometimes been suggested to be phenotypical variations of DSH.
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