Atypical skin conditions of the neck and back as a dermal manifestation of anti-HMGCR antibody-positive myopathy.

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy (IIM). Though patients with IMNM were not considered to show skin rash, several reports have showed atypical skin conditions in patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive IMNM (HMGCR-IMNM). The incidence and phenotype of skin conditions in patients with HMGCR-IMNM are not fully known. RESULTS: Among the 100 IIM patients diagnosed from April 2015 through August 2022, 34 (34%) presented some form of skin condition, with 27 having typical skin rashes; this included 13 patients with dermatomyositis (DM), 8 with anti-synthetase syndrome (ASS), and 6 with IMNM. Meanwhile, 8 of 19 patients with HMGCR-IMNM (42%) presented atypical skin lesions, but no patients with other IIMs did (p < 0.001). Skin eruption with ash-like scales was observed in four HMGCR-IMNM patients, and non-scaly red patches and lumps in the other four patients; accordingly, their skin manifestations were considered as other dermal diseases except for IIM. However, skin and muscle biopsies revealed the atypical skin conditions of patients with HMGCR-IMNM to have the same pathological background, formed by Bcl-2-positive lymphocyte infiltrations. CONCLUSIONS: HMGCR-IMNM patients frequently have atypical skin conditions of the neck and back. Skin biopsy specimens from these lesions showed the same Bcl-2-positive lymphocytic infiltrations as muscle biopsy specimens regardless of the different gross dermal findings. Thus, such atypical skin conditions may be suggestive for HMGCR-IMNM.

Complete Genome Sequence of Sphingomonas paucimobilis Strain Kira, Isolated from Human Neuroblastoma SH-SY5Y Cell Cultures Supplemented with Retinoic Acid.

Because of its small size, Gram-negative Sphingomonas paucimobilis can pose a risk of nosocomial infection. We report the complete circular genome sequence of S. paucimobilis strain Kira, which was isolated from retinoic acid-supplemented SH-SY5Y human cell cultures, to be 3,917,410 bp (G+C content, 65.7%; 3,672 protein-coding sequences), with two plasmids (79,575 bp and 44,333 bp).

Asymptomatic coronary aneurysms in a patient with eosinophilic granulomatosis with polyangiitis who developed a digital gangrene.

A 33-year-old male with a history of bronchial asthma and allergic rhinitis was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) eight years ago. The diagnosis was based on the presence of fever, remarkable eosinophilia, and painful digital ulcer. His signs and symptoms improved with a moderate dose of glucocorticoids. Thereafter, he was lost to follow-up, failing to attend any of the scheduled appointments. Three years later, he presented with painful digital gangrene on the lateral fold of the right ring fingernail and abdominal pain triggered by meals. Angiography showed multiple occlusions and severe stenoses of the peripheral arteries and coronary aneurysms, which confirmed the diagnosis of medium vessel vasculitis of the coronary and peripheral arteries due to flare up of EGPA. EGPA predominantly affects the small-sized vessels, but rarely the medium-sized vessels. Coronary vasculitis might occur asymptomatically, until the coronary stenosis becomes severe or myocardial infarction develops; hence, its prevalence is underestimated. In this case, a digital gangrene prompted us to perform a systemic angiography, leading to the diagnosis of coronary vasculitis. Careful observation for coronary lesions is necessary in patients with EGPA who develop digital gangrene.

Hypocomplementemic cutaneous small vessel vasculitis in a patient with IgG4-related disease.

A 62-year-old man was diagnosed with IgG4-related disease based on multiple sites of lymphadenopathy, lymph node biopsy, and elevated serum levels of IgG4. Hypocomplementemia was also observed. During admission, he was referred to our department complaining of multiple areas of purpura on the lower legs. Histological examination revealed leukocytoclastic vasculitis with fibrinoid necrosis, neutrophil infiltration, and nuclear dust in the upper dermis. To date, only a few cases of cutaneous vasculitis have been reported in IgG4-related disease, all of which showed hypocomplementemia. The role of IgG4 in the etiology of leukocytoclastic vasculitis in IgG4-related disease remains unknown and further studies are necessary.

Association of host immunity with Helicobacter pylori infection in recurrent gastric cancer.

BACKGROUND: Helicobacter pylori infection is associated with the incidence of gastric cancer. Endoscopic resection has been developed as a proper technique to treat early stage of gastric cancer. However, some patients develop recurrent gastric cancer within 5 years after endoscopic treatment. The aim of the present study is to explore a biomarker for detecting people who has high risk of gastric cancer recurrence. METHODS: We analyzed the Interleukin-10 (IL-10) single nucleotide polymorphism (SNP) and IgG subclass responses to the bacteria in patients with early gastric cancer and recurrent gastric cancer. RESULTS: Patients with hetero-type in the 1082 SNP and CC genotype in the 592 SNP were at high risk of recurrence of gastric cancer. In patients with genotype carrying high risk of recurrence, IgG1 level tended to be higher than that in patients with other genotypes. CONCLUSIONS: Dominance of T helper 2 (Th2) immunity controlled by IL-10 cytokine may be associated with H. pylori-associated gastric cancer recurrence.

Production of Cisplatin-Incorporating Hyaluronan Nanogels via Chelating Ligand-Metal Coordination.

Hyaluronan (HA) is a promising drug carrier for cancer therapy because of its CD44 targeting ability, good biocompatibility, and biodegradability. In this study, cisplatin (CDDP)-incorporating HA nanogels were fabricated through a chelating ligand-metal coordination cross-linking reaction. We conjugated chelating ligands, iminodiacetic acid or malonic acid, to HA and used them as a precursor polymer. By mixing the ligand-conjugated HA with CDDP, cross-linking occurred via coordination of the ligands with the platinum in CDDP, resulting in the spontaneous formation of CDDP-loaded HA nanogels. The nanogels showed pH-responsive release of CDDP, because the stability of the ligand-platinum complex decreases in an acidic environment. Cell viability assays for MKN45P human gastric cancer cells and Met-5A human mesothelial cells revealed that the HA nanogels selectively inhibited the growth of gastric cancer cells. In vivo experiments using a mouse model of peritoneal dissemination of gastric cancer demonstrated that HA nanogels specifically localized in peritoneal nodules after the intraperitoneal administration. Moreover, penetration assays using multicellular tumor spheroids indicated that HA nanogels had a significantly higher ability to penetrate tumors than conventional, linear HA. These results suggest that chelating-ligand conjugated HA nanogels will be useful for targeted cancer therapy.

A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response.

Diacylglycerol kinase (DGK) consists of 10 isozymes. The α-isozyme enhances the proliferation of cancer cells. However, DGKα facilitates the nonresponsive state of immunity known as T-cell anergy; therefore, DGKα enhances malignant traits and suppresses immune surveillance. The aim of this study was to identify a novel small molecule that selectively and potently inhibits DGKα activity. We screened a library containing 9,600 chemical compounds using a newly established high-throughput DGK assay. As a result, we have obtained a promising compound, 5-[(2E)-3-(2-furyl)prop-2-enylidene]-3-[(phenylsulfonyl)amino]2-thioxo-1,3-thiazolidin-4-one) (CU-3), which selectively inhibited DGKα with an IC50 value of 0.6 µM. CU-3 targeted the catalytic region, but not the regulatory region, of DGKα. CU-3 competitively reduced the affinity of DGKα for ATP, but not diacylglycerol or phosphatidylserine. Moreover, this compound induced apoptosis in HepG2 hepatocellular carcinoma and HeLa cervical cancer cells while simultaneously enhancing the interleukin-2 production of Jurkat T cells. Taken together, these results indicate that CU-3 is a selective and potent inhibitor for DGKα and can be an ideal anticancer drug candidate that attenuates cancer cell proliferation and simultaneously enhances immune responses including anticancer immunity.

Preparation of uniform-sized hemoglobin-albumin microspheres as oxygen carriers by Shirasu porous glass membrane emulsification technique.

We have developed a new type of artificial oxygen carrier composed of bovine hemoglobin (bHb) and bovine serum albumin (BSA) prepared by Shirasu porous glass (SPG) membrane emulsification technique. The resultant emulsion droplets containing 10 wt% bHb and 5-20 wt% BSA were subsequently cross-linked by glutaraldehyde to form the microspheres. Due to the uniform pore structure of SPG membranes, the average diameters of bHb10-BSAm microspheres were successfully controlled at around 5 µm with a coefficient of variation of around 10%. In addition, the biocompatibility of the carriers depended on their oxyhemoglobin percentage regardless of their same size. Finally, the P50 values of these microspheres ranged from 8.08 to 11.60 mmHg, which showed a high oxygen affinity and an oxygen delivery function.