The aim of the measurement of Epstein‐Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites

Epstein‐Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut‐off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell‐free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell‐free EBV DNA in plasma might be related to cytolysis such as that observed in HLH

Increase of DC-LAMP+ mature dendritic cell subsets in dermatopathic lymphadenitis of mycosis fungoides

Background: Little is known about the immunological milieu of the skin-draining lymph nodes (LNs) in mycosis fungoides (MF). Objectives: We studied dendritic cell (DC) subsets in the dermatopathic lymphadenitis of MF patients. Methods: We immunohistochemically examined DC subsets and their distribution in 16 LN samples from 14 patients with MF (N1 LN, eight patients; N2, four; and N3, four), and we compared them with non-metastatic sentinel LNs from eight patients with melanoma. Results: The number of S-100 protein+ DCs was markedly increased in the LNs from the MF patients and the major component was DC-LAMP+ mature DCs in the outer and paracortex areas, where DC-SIGN+ immature DCs were relatively decreased in proportion. In contrast, DC-SIGN+ cells were relatively increased in proportion compared to DC-LAMP+ cells in the medulla. Although no significant difference was observed in the proportions of CD1a+ or Langerin+ DCs among the N1, N2, and N3 nodes, CD163+ M2-type macrophages were increased in number in the N2 and N3 nodes. Conclusions: Our observations indicate that mature DCs accumulate in the outer and paracortex areas in dermatopathic lymphadenitis and M2-type macrophages might increase in number during disease progression

An Intuitive, Informative, and Most Balanced Representation of Phylogenetic Topologies

The recent explosion in the availability of genetic sequence data has made large-scale phylogenetic inference routine in many life sciences laboratories. The outcomes of such analyses are, typically, a variety of candidate phylogenetic relationships or tree topologies, even when the power of genome-scale data is exploited. Because much phylogenetic information must be buried in such topology distributions, it is important to reveal that information as effectively as possible; however, existing methods need to adopt complex structures to represent such information. Hence, researchers, in particular those not experts in evolutionary studies, sometimes hesitate to adopt these methods and much phylogenetic information could be overlooked and wasted. In this paper, we propose the centroid wheel tree representation, which is an informative representation of phylogenetic topology distributions, and which can be readily interpreted even by nonexperts. Furthermore, we mathematically prove this to be the most balanced representation of phylogenetic topologies and efficiently solvable in the framework of the traveling salesman problem, for which very sophisticated program packages are available. This theoretically and practically superior representation should aid biologists faced with abundant data. The centroid representation introduced here is fairly general, so it can be applied to other fields that are characterized by high-dimensional solution spaces and large quantities of noisy data. The software is implemented in Java and available via http://cwt.cb.k.u-tokyo.ac.jp/

Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times). Following treatment, liver and renal function improved and the erythema disappeared

VPS13D‐related disorders presenting as a pure and complicated form of hereditary spastic paraplegia

Abstract Background Alterations of vacuolar protein sorting‐associated protein 13 (VPS13) family members including VPS13A, VPS13B, and VPS13C lead to chorea acanthocytosis, Cohen syndrome, and parkinsonism, respectively. Recently, VPS13D mutations were identified as a cause of VPS13D‐related movement disorders, which show several phenotypes including chorea, dystonia, spastic ataxia, and spastic paraplegia. Methods We applied whole‐exome analysis for a patient with a complicated form of hereditary spastic paraplegia (HSP) and her unaffected parents. Then, we screened the candidate genes in 664 Japanese families with HSP in Japan. Results We first found a compound heterozygote VPS13D mutation and a heterozygote ABHD4 variation in a sporadic patient with spastic paraplegia. Then, we found three patients with VPS13D mutations in two Japanese HSP families. The three patients with homozygous mutations (p.Thr1118Met/p.Thr1118Met and p.Thr2945Ala/p.Thr2945Ala) in the VPS13D showed an adult onset pure form of HSP. Meanwhile, the patient with a compound heterozygous mutation (p.Ser405Arg/p.Arg3141Ter) in the VPS13D showed a childhood onset complicated form of HSP associated with cerebellar ataxia, cervical dystonia, cataracts, and chorioretinal dystrophy. Conclusion In the present study, we found four patients in three Japanese families with novel VPS13D mutations, which may broaden the clinical and genetic findings for VPS13D‐related disorders