Clinical importance of anti-Ro52 antibody in polymyositis and dermatomyositis.

Objectives: To clarify the clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM).

Methods: We retrospectively examined the clinical features and status of anti-Ro52 Abs in patients with PM/DM admitted to the University of Tsukuba Hospital between January 2019 and February 2023. We compared the anti-Ro52 Ab-positive and anti-Ro52 Ab-negative groups.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4 plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy.

Multidrug-resistant IgA Vasculitis with Gastrointestinal Symptoms Successfully Treated with Intravenous Cyclophosphamide and Maintained with Mycophenolate Mofetil.

We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

Objectives: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX).

Methods: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups.

Predictive Factors for Pneumomediastinum During Management of Connective Tissue Disease-related Interstitial Lung Disease: A Retrospective Study.

Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49).

QTc interval prolongation in patients with systemic lupus erythematosus treated with hydroxychloroquine.

Objectives: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation.

Methods: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group).

Clinical features of large vessel vasculitis (LVV): Elderly-onset versus young-onset.

Objectives: We compared large vessel vasculitis (LVV) clinical features between age groups.

Methods: We retrospectively examined clinical features and therapies in 41 LVV patients at our hospital from January 2010 to March 2020. We compared two patient groups, elderly (≥50 years) and young (<50 years).

Clinical features and prognosis of nocardiosis in patients with connective tissue diseases.

Objectives: To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs).

Methods: We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes.

A Comparison of PMDA and EMA Consultations for Regulatory and Scientific Matters in Drugs and Regenerative Medicine Products.

The Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA) have provided a wide range of regulatory and scientific consultation menus to cover any development stage of drugs and regenerative medicine products, respectively. The current study compares Consultations by PMDA and Scientific Advice by EMA in terms of consultation types, consultation performances, and specific consultation procedures with timelines. Each agency sets intensive but highly professional procedures and timelines in order to provide sufficient advice in a timely manner.

Arsenic trioxide inhibits human t cell-lymphotropic virus-1-induced syncytiums by down-regulating gp46.

Adult T-cell leukemia (ATL) is a severe chemotherapy-resistant malignancy associated with prolonged infection by the human T cell-lymphotropic virus 1 (HTLV-1). One approach to prevent the onset of ATL is to inhibit the growth/transmission of HTLV-1 infected cells using arsenic trioxide (As(2)O(3)). However, there are no reports on the transmission inhibitory effect of As(2)O(3).

The augmentation of intracellular delivery of peptide therapeutics by artificial protein transduction domains.

Protein transduction domains (PTDs), such as HIV-derived Tat, have been successfully used as functional biomaterials for intracellular delivery of anti-cancer macromolecular drugs (protein, peptides, and oligonucleotides). Although there were therefore great expectations regarding the therapeutic potential of PTDs for the development of anti-cancer therapeutics, their clinical application so far has been extremely limited because of the relatively high concentrations required to mediate any effects on cancer cells in vitro or in vivo. In this context, improving the transduction efficiency of PTDs using phage display-based molecular evolution techniques may be useful for creating artificial PTDs with high efficiency and safety.

Organelle-targeted delivery of biological macromolecules using the protein transduction domain: potential applications for Peptide aptamer delivery into the nucleus.

Extensive effort is currently being expended on the innovative design and engineering of new molecular carrier systems for the organelle-targeted delivery of biological cargoes (e.g., peptide aptamers or biological proteins) as tools in cell biology and for developing novel therapeutic approaches.

Combination of two fiber-mutant adenovirus vectors, one encoding the chemokine FKN and another encoding cytokine interleukin 12, elicits notably enhanced anti-tumor responses.

For achieving optimal cancer immunotherapy, it is anticipated that both the activation and infiltration of immune cells into tumor are indispensable. In the present study, fiber-mutant adenovirus vectors (Ad) encoding chemokine FKN, (AdRGD-FKN), and cytokine interleukin 12, (AdRGD-IL-12), were constructed. The in vivo gene expression of AdRGD was confirmed and the combination of both FKN and IL-12 encoding Ad elicited synergistic anti-tumor activity in ovarian carcinoma, which induced tumor regression in all tumor-bearing mice, while using FKN alone did not show notable tumor-suppressive effect.

Creation and X-ray structure analysis of the tumor necrosis factor receptor-1-selective mutant of a tumor necrosis factor-alpha antagonist.

Tumor necrosis factor-alpha (TNF) induces inflammatory response predominantly through the TNF receptor-1 (TNFR1). Thus, blocking the binding of TNF to TNFR1 is an important strategy for the treatment of many inflammatory diseases, such as hepatitis and rheumatoid arthritis. In this study, we identified a TNFR1-selective antagonistic mutant TNF from a phage library displaying structural human TNF variants in which each one of the six amino acid residues at the receptor-binding site (amino acids at positions 84-89) was replaced with other amino acids.

Improved cytosolic translocation and tumor-killing activity of Tat-shepherdin conjugates mediated by co-treatment with Tat-fused endosome-disruptive HA2 peptide.

Tat peptides are useful carriers for delivering biologic molecules into the cell for both functional analysis of intracellular disease-related proteins and treatment of refractory diseases. Most internalized Tat-fused cargos (Tat-cargos) are trapped within the endosome, however, which limits the biologic function of the cargo. In this study, we demonstrated that Tat-fused HA2 peptide (HA2Tat), an endosome disrupted peptide, enhanced the endosome-escape efficiency of Tat-cargos.

Creation of novel cell-penetrating peptides for intracellular drug delivery using systematic phage display technology originated from Tat transduction domain.

Many biologically active proteins need to be delivered intracellularly to exert their therapeutic action inside the cytoplasm. Cell penetrating peptides (CPPs) have been developed to efficiently deliver a wide variety of cargo in a fully biological active form into a range of cell types for the treatment of multiple preclinical disease models. To further develop this methodology, we established a systematic approach to identify novel CPPs using phage display technology.

Creation of novel Protein Transduction Domain (PTD) mutants by a phage display-based high-throughput screening system.

Significant research effort is currently focused on Protein Transduction Domains (PTDs) as potential intracellular drug delivery carriers. However, the application of this technology is limited because the transduction efficiencies are often insufficient for therapeutic purposes, even using HIV-1 Tat peptide. Here we describe a high-throughput screening method based on a phage display system for isolating novel PTDs with improved cell penetration activity.

Quality enhancement of the non-immune phage scFv library to isolate effective antibodies.

The non-immune phage antibody library system is one of the most attractive technologies available to current therapeutic, diagnostic and basic scientific research. This system allows the rapid isolation of antibodies of interest that could subsequently be applied directly to drug delivery systems and antibody therapy. Previously, we reported the primer sets to encompass the antibody repertoire and thus improve library quality.

A novel method for construction of gene fragment library to searching epitopes.

Identification of the epitope sequence or the functional domain of proteins is a laborious process but a necessary one for biochemical and immunological research. To achieve intensive and effective screening of these functional peptides in various molecules, we established a novel screening method using a phage library system that displays various lengths and parts of peptides derived from target protein. Applying this library for epitope mapping, epitope peptide was more efficiently identified from gene fragment library than conventional random peptide library.

Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector.

Considerable attention has recently been paid to the application of chemokines to cancer immunotherapy because of their chemotactic affinity for a variety of immune cells and because several chemokines are strongly angiostatic. In the present study, the recombinant adenovirus vectors encoding chemokine CCL19 or XCL1 in an E1 cassette (AdRGD-mCCL19 and AdRGD-mXCL1) were developed. The constructed fiber-mutant adenovirus vector, which contained the integrin-targeting Arg-Gly-Asp (RGD) sequence in the fiber knob, notably enhanced the transfection efficiency to OV-HM ovarian carcinoma cells compared to that induced by conventional adenovirus vector.

A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma.

Cytokine-encoding viral vectors are considered to be promising in cancer gene immunotherapy. Interleukin 12 (IL-12) has been used widely for anti-tumor treatment, but the administration route and tumor characteristics strongly influence therapeutic efficiency. Meth-A fibrosarcoma has been demonstrated to be insensitive to IL-12 treatment via systemic administration.

Fusogenic liposome can be used as an effective vaccine carrier for peptide vaccination to induce cytotoxic T lymphocyte (CTL) response.

We reported previously that fusogenic liposome (FL) introduced antigen protein encapsulated in the liposome directly into the cytoplasm of the antigen presenting cells, and that it induced immune responses. In the present study, we encapsulated TAX38-46, an HTLV-I derived protein and an antigen peptide model, into FL. The ability to induce effective cytotoxic T lymphocytes (CTL) responses in immunized mice was evaluated.

Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine.

In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro.