Anti-glycopeptide mAb LpMab-21 against Podoplanin

Human podoplanin (hPDPN), which binds to C‐type lectin‐like receptor‐2 (CLEC‐2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer‐associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung‐type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mA bs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti‐hPDPN mA b, LpMab‐21. To characterize the hPDPN epitope recognized by the LpMab‐21, we established glycan‐deficient CHO‐S and HEK‐293T cell lines, using the CRISPR/Cas9 or TALEN. Flow cytometric analysis revealed that the minimum hPDPN epitope, in which sialic acid is linked to Thr76, recognized by LpMab‐21 is Thr76–Arg79. LpMab‐21 detected hPDPN expression in glioblastoma, oral squamous carcinoma, and seminoma cells as well as in normal lymphatic endothelial cells. However, LpMab‐21 did not react with renal glomerular epithelial cells or lung type I alveolar cells, indicating that sialylation of hPDPN Thr76 is cell‐type‐specific. LpMab‐21 combined with other anti‐hPDPN antibodies that recognize different epitopes may therefore be useful for determining the physiological function of sialylated hPDPN

Recombinant human FGF-2 for the treatment of early-stage osteonecrosis of the femoral head: TRION, a single-arm, multicenter, Phase II trial

Aim: This study aimed to evaluate the 2-year outcomes from a clinical trial of recombinant human FGF-2 (rhFGF-2) for osteonecrosis of the femoral head (ONFH). Patients & methods: Sixty-four patients with nontraumatic, precollapse and large ONFHs were percutaneously administered with 800 μg rhFGF-2 contained in gelatin hydrogel. Setting the end point of radiological collapse, we analyzed the joint preservation period of the historical control. Changes in two validated clinical scores, bone regeneration and safety were evaluated. Results: Radiological joint preservation time was significantly higher in the rhFGF-2 group than in the control group. The ONFHs tended to improve to smaller ONFHs. The postoperative clinical scores significantly improved. Thirteen serious adverse events showed recovery. Conclusion: rhFGF-2 treatment increases joint preservation time with clinical efficacy, radiological bone regeneration and safety

An Ultra-Broad-Band Reflection-Type Phase-Shifter MMIC With Series and Parallel LC Circuits

Abstract-An ultra-broad-band reflection-type phase shifter is proposed. Theoretically, the proposed phase shifter has frequency-independent characteristics in the case of 180 phase shift. The phase shifter is composed of a 3-dB hybrid coupler and a pair of novel reflective terminating circuits. The reflective terminating circuit switches two states of series and parallel LC circuits. Using an ideal circuit model without parasitic circuit elements, we have derived the determining condition of frequency independence of circuit elements. Extending the concept, we can also obtain a broad-band phase shifter for other phase difference as well. In this case, for a given phase difference and an operating frequency, we also derive a condition to obtain minimum variation of phase difference around the operating frequency. This enables the broad-band characteristics for arbitrary phase difference. Index Terms-Broad-band, MMIC, monolithic microwave integrated circuit, phase shifter, reflection type

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

A 6-18 GHz 5-Bit Phase Shifter MMIC Using Series/Parallel LC Circuit

A high performance 6-18 GHz 5-bit reflection type phase shifter MMIC is presented. It employs a novel ultra-broad-band circuit design technique utilizing a series/parallel LC circuit for an 180 o phase shift over all frequencies. The fabricated phase shifter MMIC with SPDT switch suitable for T/R modules has demonstrated a typical insertion loss of 9.4 dB +/- 1.4 dB, a maximum RMS amplitude error of 0.33 dB and a maximum RMS phase error of 7 o over entire operating bandwidths