Disseminated Histoplasmosis presenting with panniculitis and macrophage activation syndrome in a patient undergoing immunosuppressive therapy for Mixed Connective Tissue Disease (MCTD).

Histoplasmosis, a fungal infection caused by Histoplasma capsulatum, is endemic in many parts of the world. However, this is not common in Japan. We herein present a unique case of military histoplasmosis in a 45-year-old female with mixed connective tissue disease (MCTD) who was receiving immunosuppressive therapy. The histological findings coupled with molecular confirmation led to final a diagnosis. This case emphasizes the diagnostic challenges associated with histoplasmosis in immunocompromised patients and underscores the importance of considering it in the differential diagnosis of any atypical presentation in rheumatic patients.

Utility of BRAF V600E mutation-specific immunohistochemistry in detecting BRAF V600E-mutated gastrointestinal stromal tumors.

OBJECTIVES: As patients with BRAF V600E mutation respond to BRAF inhibitors, it is important to identify these mutations to stratify patients for the appropriate therapy. In this study, we evaluated the utility of a BRAF V600E allele-specific antibody in gastrointestinal stromal tumors (GISTs). METHODS: BRAF V600E mutation-specific immunohistochemistry (negative, weak, or moderate/strong expression) and BRAF sequencing were performed on 38 consecutive GISTs diagnosed between January 2013 and April 2014. RESULTS: GISTs from a cohort of 25 men and 13 women (mean age, 61 years; range, 39-88 years) were localized to the stomach (18), small bowel (10), colon (three), rectum (two), and pelvis/omentum (five). Strong and diffuse cytoplasmic BRAF expression was noted in two (5%) of 38 cases, while eight (21%) of 38 cases showed weak staining, and 28 (74%) of 38 cases were negative. Both of the strongly positive cases arose in the stomach, occurring in a 42-year-old and a 47-year-old woman, respectively. The lesions measured 0.8 and 1 cm, showed spindle cell morphology, and had no risk of progressive disease by Miettinen criteria. Both cases showed heterozygous BRAF V600E, while no BRAF mutations were detected in cases with weak or negative BRAF expression. CONCLUSIONS: BRAF V600E mutation-specific immunohistochemistry is a highly sensitive and specific method for detecting BRAF-mutated GISTs.

[Case of microscopic polyangiitis and giant cell arteritis after influenza vaccination].

We report a case of microscopic polyangiitis (mPA) and giant cell arteritis (GCA) (polyangiitis overlap syndrome) after influenza vaccination. A 67-year-old female with chronic kidney disease, who had been observed by a physician, presented fever and headache after immunization of influenza vaccine. She was diagnosed as having with mPA and GCA based on symptoms, worsening of renal function, biopsy of temporal artery (giant cell arteritis) and skin (microscopic polyangiitis), pulmonary involvement and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). She was treated with prednisolone (PSL) and the symptoms were improved. However, two months later she was presented with general physical weariness. She was diagnosed as having with pneumocystis pneumonia, cytomegalovirus infection and cryptococcosis. Despite intensive treatment, she was died and autopsy was performed. The present case suggests that the influenza vaccination may cause different types of vasculitis, mPA and GCA, through the common mechanism in pathophysiology. This patient is also the first case of mPA and GCA proven by histological examination.

The primitive rhodophyte Cyanidioschyzon merolae contains a semiamylopectin-type, but not an amylose-type, alpha-glucan.

The storage glucans of Cyanidioschyzon merolae [clade L-1 (cyanidian algae), order Porphyridiales, subclass Bangiophycidae], which is considered to be one of the most primitive rhodophytes, were analyzed to understand the early evolution of the glucan structure in the Rhodophyta. Chain-length distribution analysis of the glucans of cyanidian algae demonstrated that while the glucans of Cyanidium caldarium and Galdieria sulphuraria are of the glycogen type, those of C. merolae are of the semiamylopectin type, as in other lineages of the Rhodophyta. Gel permeation chromatography, however, showed that the glucans of C. merolae do not include amylose, being different from those of other Bangiophycidae species. Identification by MALDI-TOF-MS and enzyme assaying of glucan granule-bound proteins indicated that phosphorylase, but not starch synthase, is included. Thus, C. merolae has an unusual glucan and bound-protein composition for the Bangiophycidae, appearing to be a member of the Florideophycidae. The finding that the alga does not contain amylose or the related enzyme, granule-bound starch synthase, is, however, consistent with previously reported results of molecular phylogenetic analysis of starch synthases. Our results support an evolutionary scenario defined by the loss of starch and reversion to glycogen synthesis during the evolution of cyanidian algae, and suggest the possibility that a C. merolae-like primitive rhodophyte might have evolved into the Florideophycidae.

Variation in storage alpha-glucans of the Porphyridiales (Rhodophyta).

Storage glucans were analyzed in the Porphyridiales which include the most primitive and phylogenetically diverged species in the Rhodophyta, to understand early evolution of the glucan structure in the Rhodophyta. The storage glucans of both Galdieria sulphuraria and Cyanidium caldarium consisted of glycogen, while those of Rhodosorus marinus, Porphyridium purpureum, P. sordidum and Rhodella violacea could be defined as semi-amylopectin. X-ray diffraction analysis of the glucans demonstrated variation in the crystalline structure: the patterns in P. purpureum and R. violacea were of A- and B-types, respectively, while alpha-glucans of R. marinus and P. sordidum displayed structures with lower crystallinity. Electron microscopic observations indicated that the alpha-glucans of P. sordidum consisted of two kinds of granules; a minor component of more dense granules with crystalline leaflets and a major component of softer ones without crystalline structure. Gel permeation chromatography showed that all the species containing the semi-amylopectin-type glucans also contained amylose, although the relative amounts of this fraction were different depending on the species. Our results are consistent with two distinct evolution scenarios defined either by the independent acquisition of semi-crystalline starch-like structures in the different plant lineages or more probably by the loss of starch and reversion to glycogen synthesis in cyanidian algae growing in hot and acid environments.