Deoxygenative Hetero- and Carbofunctionalizations of Diarylketones.

Direct transformations of diarylketones to hetero- and carbofunctionalized diarylmethanes have been developed. The reactions involve a phospha-Brook rearrangement of diphenylphosphine oxide with diarylketones, followed by substitutions with various nucleophiles such as amides, amines, phenols, thiols, and diborylmethane under palladium catalysis to afford the corresponding functionalized diarylmethanes in a reductive manner.

Sjögren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development.

Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammation with lymphoid infiltration and destruction of the salivary glands. Although many genome-wide association studies have revealed disease-associated risk alleles, the functions of the majority of these alleles are unclear. Here, we show previously unrecognized roles of GTF2I molecules by using two SS-associated single nucleotide polymorphisms (SNPs), rs73366469 and rs117026326 (GTF2I SNPs). We found that the risk alleles of GTF2I SNPs increased GTF2I expression and enhanced nuclear factor-kappa B (NF-κB) activation in human salivary gland cells via the NF-κB p65 subunit. Indeed, the knockdown of GTF2I suppressed inflammatory responses in mouse endothelial cells and in vivo. Conversely, the over-expression of GTF2I enhanced NF-κB reporter activity depending on its p65-binding N-terminal leucine zipper domain. GTF2I is highly expressed in the human salivary gland cells of SS patients expressing the risk alleles. Consistently, the risk alleles of GTF2I SNPs were strongly associated with activation of the IL-6 amplifier, which is hyperactivation machinery of the NF-κB pathway, and lymphoid infiltration in the salivary glands of SS patients. These results demonstrated that GTF2I expression in salivary glands is increased in the presence of the risk alleles of GTF2I SNPs, resulting in activation of the NF-κB pathway in salivary gland cells. They also suggest that GTF2I could be a new therapeutic target for SS.

A Case of IgG4-Related Ophthalmic Disease With Coronary Arteritis.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, often with elevated serum IgG4. Multiple organs may be affected. Coronary arteritis may be one form of fatal involvement in IgG4-RD. IgG4-RD can manifest as periocular lesions, called IgG4-related ophthalmic disease (IgG4-ROD). Here, the authors describe a patient with asymptomatic coronary arteritis detected after the diagnosis of IgG4-ROD. A 58-year-old male complained of eyelid swelling and diplopia without systemic symptoms. Swelling of bilateral lacrimal glands and infraorbital nerves, high serum IgG4 levels, and histopathology of lacrimal gland tissue fulfilled diagnostic criteria for IgG4-ROD. After diagnosis, systemic and coronary CT showed coronary lesions and coronary artery stenosis. After prednisolone at 40 mg/day was administered, swelling of the lacrimal glands, diplopia, and coronary lesions improved. This case emphasizes the importance of systemic screening, even if initial symptoms are solely associated with periocular regions.

Anti-TIF1γ antibody predicted malignancy of thymic tumor with dermatomyositis as an "autoimmune tumor marker": A case report.

RATIONALE: An association between inflammatory myopathy and malignancy has been recognized particularly in patients positive for anti-transcription intermediary factor 1γ (TIF1γ) antibody. We report a case of anti-TIF1γ antibody positive dermatomyositis (DM) associated with thymic carcinoma which radiographically mimicked benign tumor. PATIENT CONCERNS: A 72-year-old man presented typical characteristic cutaneous manifestations and proximal muscle weakness with elevated levels of myogenic enzymes. An anterior mediastinal tumor was detected by computed tomography (CT) scan and radiographically assessed to be benign with distinct borders and little enhancement. DIAGNOSES: DM with anti-TIF1γ antibody and thymic carcinoma. INTERVENTIONS: Thymic carcinoma was completely resected by surgery. DM was induced into remission with glucocorticoid treatment. OUTCOMES: The serum level of myogenic enzyme remained within normal range under low-dose glucocorticoid maintenance. No evidence of carcinoma recurrence with CT scan was observed at 1-year follow up. LESSONS: The present case indicated that anti-TIF1γ antibody would play a role as the "autoimmune tumor marker" in patients with inflammatory myopathy.