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Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte-associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune-related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre-existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a

The effect of stress concentration on the compressive failure behavior of a carbon fiber composite laminate with an open hole is experimentally and numerically studied. The aspect ratio of the elli...

A 76-year-old man was admitted to our hospital with Guillain-Barré syndrome (GBS), presenting with facial palsy, dysarthria, and dysphagia as Grade 3 immune-related adverse events (irAEs) due to pembrolizumab administration for Stage IV lung adenocarcinoma. Although prednisolone (1 mg/kg) was started for GBS due to the irAE, dark erythema and skin eruptions appeared on the patient’s torso. Then erosion was observed on 18% of the body surface area and skin biopsy was performed. Finally, the patient was diagnosed with Stevens-Johnson syndrome/toxic epidermal necrosis overlap. Intravenous immunoglobulin therapy was started, and the skin symptoms improved, with the erosion becoming epithelial. He died of aspiration pneumonia related to GBS, although his neurological symptoms had improved after steroid and intravenous immunoglobulin therapy. This is the first reported case of pembrolizumab-induced GBS and Stevens–Johnson syndrome/toxic epidermal necrosis overlap. It is necessary to be careful that the possibility of other severe irAEs may occur simultaneously.

The shoot meristem, a stem-cell-containing tissue initiated during plant embryogenesis, is responsible for continuous shoot organ production in postembryonic development. Although key regulatory factors including KNOX genes are responsible for stem cell maintenance in the shoot meristem, how the onset of such factors is regulated during embryogenesis is elusive. Here, we present evidence that the two KNOX genes STM and KNAT6 together with the two other regulatory genes BLR and LAS are functionally important downstream genes of CUC1 and CUC2, which are a redundant pair of genes that specify the embryonic shoot organ boundary. Combined expression of STM with any of KNAT6, BLR, and LAS can efficiently rescue the defects of shoot meristem formation and/or separation of cotyledons in cuc1 cuc2 double mutants. In addition, CUC1 and CUC2 are also required for the activation of KLU, a cytochrome P450-encoding gene known to restrict organ production, and KLU counteracts STM in the promotion of meristem activity, providing a possible balancing mechanism for shoot meristem maintenance. Together, these results establish the roles for CUC1 and CUC2 in coordinating the activation of two classes of genes with opposite effects on shoot meristem activity.

This study aimed to clarify the effects of counter cations on the alkaline-induced β-O-4 bond cleavage and further reactions of β-O-4-type substructures in lignin. For this purpose, a non-phenolic β-O-4-type lignin model compound, the erythro isomer of 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)propane-1,3-diol (veratrylglycerol-β-guaiacyl ether), was treated in a 100% water solution or an aqueous methanol, ethanol, or 1,4-dioxane solution containing LiOH, NaOH, or CsOH as an alkaline source at 150 °C. The rates of β-O-4 bond cleavage were in the order of CsOH > NaOH > LiOH in all solvents. This order can rationally be attributed to the strength of the interactions between HO– and the counter cations. Because Cs+ has the lowest positive charge density among the counter cations and hence interacts with HO– most weakly, HO– can exert its reactivity most actively in the reactions using CsOH. We also discuss how the counter cations affect the profile of reaction products.

The reaction products of an alkaline treatment of non-phenolic β-O-4-type lignin model compounds (C6–C2-type) consisting of p-hydroxyphenyl (H), guaiacyl (G), and/or syringyl (S) nuclei were identified and quantified. This was performed to examine how the type of H, G, or S nucleus affect the reaction product profiles. The major identified and quantified reaction products were phenol derivatives that were liberated from the aryl sides of the β-O-4 ether bonds of the lignin model compounds. Other products included derivatives of phenylethane-1,2-diol (glycol-type), benzaldehyde, and acetophenone, which originated from the alkyl sides of the β-O-4 ether bonds of the lignin model compounds. Although the type of aromatic nucleus of the aryl side of the β-O-4 ether bond of the lignin model compounds did not significantly affect the profile of the reaction products, the type of the alkyl side nucleus was influential. The glycol-type compound was the exclusive major reaction product when the S nucleus was on the alkyl side of the β-O-4 ether bond. On the other hand, when the H or G nucleus was present, a benzaldehyde derivative was the other major reaction product.

This study aimed to clarify why the β-O-4 bond cleavage of syringyl lignin is more rapid than that of guaiacyl lignin under alkaline pulping conditions. We examined whether or not three chemical factors, acidity of the α-hydroxy group, nucleophilicity of the generated α-alkoxide, and leaving ability of the leaving phenoxide, are different between syringyl and guaiacyl lignins and control the rate of the alkaline-induced β-O-4 bond cleavage, employing dimeric non-phenolic β-O-4-type lignin model compounds (LMCs) and novel methods for estimating these three factors. The results indicated that the α-hydroxy groups of syringyl-type LMCs are relatively more acidic than those of guaiacyl-type and that syringyl nucleus is a better leaving group than guaiacyl nucleus in the β-O-4 bond cleavage. These factors result in the β-O-4 bond of syringyl lignin being more prone to the alkaline-induced cleavage than that of guaiacyl lignin.

This is a disseminated maculopapular rash due to trichinellosis in a woman in her 50s, secondary to eating undercooked meat (fig 1). She presented at the dermatology department with a 10 day history of pyrexia, eosinophilia, malaise, and abdominal …

A 32-year-old Japanese man presented to our hospital with a 5-month history of painful nodules on the fingers. He had previously developed left atrial myxoma followed by cerebral embolism and had undergone resection of the cardiac tumor 4 months before his first visit. His family history was unremarkable. Physical examination showed subcutaneous nodules 4 to 17 mm in size on all finger pads (Figure 1A and 1B). The tumors were smooth and as hard as cartilage. Hand radiographs showed irregularly shaped subcutaneous calcification corresponding to the nodules (Figure 2), and postoperative examination of the 3-dimensional computed tomographic reconstruction indicated the tumors more clearly (Figure 3). Physical examination and diagnostic imaging detected no tumors in other sites, including the lower extremities. The blood test results, including endocrine examination, were unremarkable. Figure 1. Subcutaneous nodules on all finger pads: the left …

Granuloma faciale (GF) is an uncommon inflammatory dermatosis that is characterized by one or several asymptomatic brown red nodules or plaques usually occurring on the face. GF is known to be extremely resistant to treatment. Various treatments have been attempted, including topical or intralesional or systemic corticosteroids, dapsone, antimalarials, colchicine, topical tacrolimus, and topical psoralen; however, none of these have been found to be reliably efficacious. We tried numerous combinations and rotations of therapeutic modalities for GF over a long time. We described a case of GF in which the eruptions were carefully observed over the course of 14 years before finally resolving. Our experience suggests that continuous and careful follow-up, and trials of combinations and rotations of therapeutic modalities are essential for treating GF.

Background Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP180 is the primary autoantigen of BP, and in a portion of BP cases, BP230 is the only target of autoantibodies. Such BP is called BP230-type BP. BP230-type BP tends to show milder clinical phenotypes than conventional BP, but the reason is unclear. The pathogenic roles of autoantibodies and complement activation have been shown in conventional BP, but the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP remain unclear. Objective To compare the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP with those in conventional BP with autoantibodies to BP180 and BP230 (BP180-BP230-type BP). Methods The diagnosis of BP was confirmed by the histopathology of the lesions, the deposition of IgG and complement in the perilesional skin and the presence of circulating autoantibodies to BP180 and BP230. The disease severity was determined by bullous pemphigoid disease area index. The deposition of IgG subclasses and complement deposition were examined by direct immunofluorescence of the perilesional skin in 6 BP230-type BP cases and 11 BP180-BP230-type BP cases. Results Sixty seven percent of BP230-type BP cases show a mild clinical phenotype. All BP230-type BP cases and 82% of BP180-BP230-type BP cases were found to demonstrate the clear deposition of IgG4 at the basement membrane zone of skin specimens. Notably, the deposition of IgG1 and IgG3 was faint or negative in all of the BP230-type BP cases, whereas they were clearly detected in 91% and 64% of the BP180-BP230-type BP cases, respectively. The deposition of complement C3 tended to be weaker in BP230-type BP than in BP180-BP230-type BP. Conclusion The mild clinical phenotype of BP230-type BP may correlate with the weaker deposition of IgG1, IgG3 and complement in the skin lesions.

Several C6–C3 and C6–C2-type dimeric non-phenolic β-O-4 lignin model compounds, whose aromatic nuclei consisting of the carbon skeleton and β-O-4 linkage are named the A- and B-rings, respectively, were treated under alkaline pulping conditions to examine whether or not the substitution of methoxyl group on the B-ring or of guaiacyl for syringyl A-ring accelerates the β-O-4 cleavage as a further study of our previous reports. It was suggested that either first or second substitution of methoxyl group on the B-ring accelerates the β-O-4 cleavage in both C6–C3 and C6–C2 compounds although the former compounds are more sensitive to the substitution than the latter, suggesting that the lack of the γ-hydroxymethyl group makes model compound insensitive to the substitution. It was confirmed that the substitution of guaiacyl for syringyl A-ring accelerates the β-O-4 cleavage in both C6–C3 and C6–C2 compounds with the degrees similar to each other regardless of the type of the B-ring. It was clarified that the leaving ability of the leaving B-ring phenoxides in the β-O-4 cleavage does not correlate well with the pK a values of the conjugate acids of the phenoxides, which is not in accordance with the common property of a nucleophilic substitution reaction.

Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss-of-function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis-based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame-shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low-dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.

Background/purpose We report the current status of patients who underwent augmentation cystoplasty (AC) at least 20 years previously. Methods Surgical history, incidence of urinary tract infection (UTI) and bladder stones, vesicoureteral reflux (VUR), urine cytology, renal function, a colon cancer tumor marker (carcinoembryonic antigen: CEA), and patient outcomes were assessed. Results Forty patients who underwent AC (mean age: 34.4 years; mean follow-up time: 24.3 years) were analyzed. Mean age at AC was 11 years. Incidence of bladder stones was 30%. There were no incidences of carcinoma after AC, and CEA levels were not increased. Ureteral reimplantation (URI) was performed in 21 patients. URI performed at the same time as AC was successful in 14 cases (93%) and unsuccessful in 1 (7%) because of persistent VUR. UTI developed after AC in only 1 patient (2.5%) with persistent VUR. This patient required unilateral nephrectomy 18 years after the AC because of repeated UTIs. Thirty-four patients (85%) were employed, and 4 (10%) were married. Two of the 19 female patients (11%) had experienced pregnancy and delivery. Five patients (13%) had mental disorders. Conclusion Ultra long-term follow-up suggests that AC is a safe procedure with manageable sequelae, although some mental health issues remain. Type of study Case series with no comparison group. Level of evidence Level IV.

Introduction. Corynebacterium ulcerans (C. ulcerans) is a zoonotic pathogen that occasionally causes diphtheria-like symptoms in humans. Cases of C. ulcerans infection have been increasing in recent years, and C. ulcerans has been recognized as an emerging pathogen. Case presentation. Here we report a case of asphyxia death due to pseudomembrane caused by diphtheria toxin (DT)-producing C. ulcerans. This is, to our knowledge, the first fatal case of C. ulcerans infection in Japan. A strain of C. ulcerans was obtained from the patient’s pet cat and was confirmed to be identical to the patient’s isolate by sequencing of the 16S rRNA gene and the DT gene, by pulsed-field gel electrophoresis (PFGE) and by ribotyping. In the same way, it was revealed that the isolate in this case belonged to the same molecular type as the C. ulcerans 0102 isolated from the first case in Japan in a distant prefecture 15 years earlier, in 2001. Conclusion. DT-producing C. ulcerans can be contracted from a companion animal and causes human death if the appropriate treatment is delayed. The finding indicates that this molecular type of virulent C. ulcerans is currently widespread in Japan.

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BRAF inhibitors have been licensed for the treatment of unresectable or metastatic BRAF-mutated melanomas. In Japan, the BRAF inhibitor vemurafenib has been available since December 2014. Several adverse events induced by BRAF inhibitors have been reported, such as Stevens-Johnson syndrome, toxic epidermal necrosis, squamous cell carcinoma, secondary melanoma, and hand-foot syndrome. Recently, inflammatory skin lesions clinically resembling erythema nodosum have been reported as side effects that may lead to treatment discontinuation. In this report, we described the first Japanese case of erythema nodosum-like lesions induced by vemurafenib and discussed the countermeasures to this adverse reaction. Dose reduction or interruption of BRAF inhibitors should be considered on a case-by-case basis because the condition may resolve spontaneously or under symptomatic treatment. We postulate that erythema nodosum-like lesions can be controlled by careful follow-up and supportive care.

In recent years, cases of IgG/IgA pemphigus, a rare subtype of pemphigus characterized by circulating IgG and IgA autoantibodies against the keratinocyte cell surface have been reported.1-6 The cutaneous manifestations of IgG/IgA pemphigus were reported to resemble those of IgA pemphigus in form, including the presence of pustules and annular lesions.1 However, no consensus on what eruptions are typical of IgG/IgA pemphigus has been established, due to the rarity of this disease. In this report, we describe a case of IgG/IgA pemphigus who developed severe crusted lesions on the seborrheic area that closely resembled facial crusted impetigo. This article is protected by copyright. All rights reserved.

In January 2014, a 34-year-old man was referred to our hospital with hypothermia and mental fog. Clinical examination revealed his legs to be dirty, foul-smelling, red and covered with exudate and accumulated scurf that formed granular brown plaques (figure 1A). Pink nodules were aggregated into cauliflower-like plaques on the ankle joints (figure 1B). The histopathology of a biopsy specimen taken from the dorsal aspect of the ankle joint showed hyperkeratosis, pseudoepitheliomatous hyperplasia, [...]