Complete Regression of Endobronchial Carcinoid Tumor after an Endoscopic Biopsy.

An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.

Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer.

AIMS: Durvalumab (Durva) administration after chemoradiation therapy (CRT) in locally advanced non-small-cell lung cancer (NSCLC) is the standard of care, associated with relatively prolonged progression-free (PFS) and overall survival. However, pneumonitis occurs in 73.6% of Japanese patients. This retrospective study aimed to identify factors associated with Durva efficacy and safety, specifically, the risk of pneumonitis. METHODS: This study included data from 26 consecutive patients with locally advanced NSCLC who underwent CRT followed by Durva. The rates of adverse events and PFS were examined. RESULTS: The median PFS time was 15.6 months (95% confidence interval [CI]: 8.7-not available). Patients developed pneumonitis of grade 1, 2, 3, and 4 at the rate of 62%, 27%, 12%, and 0%, respectively. The median PFS time was 6.4 months for patients with programmed death ligand 1 (PD-L1) expression level of <50% and not reached for patients with PD-L1 expression level of ≥50% (hazard ratio [HR], 0.19; 95% CI: 0.04-0.89), which was significantly prolonged. The cumulative incidence of pneumonitis grade 2 or above was significantly higher when the time between the last day of thoracic radiotherapy (TRT) and the start of Durva therapy was within 14 days compared to >14 days (HR: 0.19; 95% CI: 0.06-0.59). This association was statistically significant in multivariate analysis. CONCLUSIONS: The initiation of Durva therapy within 14 days after TRT may increase the risk of pneumonitis grade 2 or above. Careful observation and suitable treatment are recommended.

A Case of Mediastinal Localized Malignant Pleural Mesothelioma Successfully Treated by Chemotherapy and Conversion Surgery.

Localized malignant mesothelioma is a rare disease and little is known about its treatment strategy. We herein report a case of localized malignant pleural mesothelioma that had infiltrated into the anterior mediastinum, which was successfully treated using chemotherapy and conversion surgery. A 63-year-old man with a mediastinal tumor was referred to our hospital. Pathologic analysis of the biopsy specimen showed malignant mesothelioma. Significant tumor shrinkage by cisplatin and pemetrexed was observed and he underwent radical surgery via a median sternotomy. The patient has been disease free for 12 months.

Severe varus knees result in a high rate of undercorrection of lower limb alignment after opening wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to clarify the indication for opening wedge high tibial osteotomy (OWHTO) in terms of lower limb alignment to achieve satisfactory clinical results. METHODS: Ninety-two patients (98 knees) with medial compartment knee osteoarthritis were investigated in this study. The average follow-up period was 34 months (range, 24-68 months). The average age of the patients at the time of surgery was 63 years (range, 41-77 years). RESULTS: The patients were divided into the following two groups according to the preoperative femorotibial angle (FTA) on anteroposterior full-length radiographs of the lower limbs while weight bearing: 29 knees with a preoperative FTA of ≥185° were defined as those with severe varus (S group), and the remaining 69 knees with a preoperative FTA of <185° were defined as those with mild varus (M group). Knees with a postoperative FTA of >175° were defined as undercorrected. The Lysholm score was used to assess the clinical results. The average postoperative FTA was 175.7° ± 4.1° in the S group and 174.6° ± 3.1° in the M group ( p = 0.013). Significantly, more undercorrected knees were observed in the S than M group ( p = 0.00035). The postoperative Lysholm score was 85.6 ± 8.5 in the S group and 88.5 ± 5.7 in the M group at the last follow-up ( p = 0.0033). CONCLUSION: Based on these results, we recommend that a preoperative FTA of <185° should be included as a criterion for OWHTO alone.

Sports and Physical Activities of Elderly Patients with Medial Compartment Knee Osteoarthritis after High Tibial Osteotomy.

OBJECTIVE: We retrospectively investigated the preoperative and postoperative sports and physical activities (SPA) of elderly patients with medial compartment knee osteoarthritis who underwent opening-wedge high tibial osteotomy (OWHTO). METHODS: Fifty-six patients (62 knees) with medial compartment knee osteoarthritis were included in the study. The patients comprised 45 women and 11 men with a mean age at surgery of 71.6 years (range, 65-81 years). The mean follow-up period was 51±7 months. Patients who performed SPA to maintain their health for at least 30 min per session more than once a week were defined as SPA cases. The preoperative and postoperative ratios of SPA cases, the time to resuming or starting postoperative SPA, and the frequency of performing postoperative SPA were investigated. Clinical results were assessed using the Lysholm score. RESULTS: Fifteen patients (26.7%) performed SPA before OWHTO and 14 (25.0%) performed SPA after OWHTO (P=0.21). The mean time to resuming or starting SPA after surgery was 14.1±10.0 months, and the frequency of postoperative SPA sessions was 4.2±2.1 per week. The mean Lysholm score significantly improved from 60.8±8.9 preoperatively to 92.5±2.5 postoperatively (P<0.0001). CONCLUSION: The ratio of patients who performed SPA after OWHTO was still <30% , and it took a comparatively long time for patients to resume or start SPA after surgery.

Deformation of the patellofemoral joint caused by synovial hemangioma: a case report.

A 15-year-old girl with synovial hemangioma of the knee joint presented with gait pain and occasional sudden swelling for over 7 years. Plain radiographs showed an irregular joint line and a lateral shift of the patella caused by malformation of the patellar groove. Arthroscopy was performed to resect the tumor and to release the lateral patellar retinaculum. If the synovial hemangioma exists in the patellofemoral joint during the growth period, we propose that early surgical treatment is necessary to avoid the deformation of the joint.

LjMATE1: a citrate transporter responsible for iron supply to the nodule infection zone of Lotus japonicus.

Symbiotic nitrogen fixation by intracellular rhizobia within legume root nodules requires the exchange of nutrients between host plant cells and their resident bacteria. While exchanged molecules imply nitrogen compounds, carbohydrates and also various minerals, knowledge of the molecular basis of plant transporters that mediate those metabolite exchanges is still limited. In this study, we have shown that a multidrug and toxic compound extrusion (MATE) protein, LjMATE1, is specifically induced during nodule formation, which nearly paralleled nodule maturation, in a model legume Lotus japonicus. Reporter gene experiments indicated that the expression of LjMATE1 was restricted to the infection zone of nodules. To characterize the transport function of LjMATE1, we conducted a biochemical analysis using a heterologous expression system, Xenopus oocytes, and found that LjMATE1 is a specific transporter for citrate. The physiological role of LjMATE1 was analyzed after generation of L. japonicus RNA interference (RNAi) lines. One RNAi knock-down line revealed limited growth under nitrogen-deficient conditions with inoculation of rhizobia compared with the controls (the wild type and an RNAi line in which LjMATE1 was not suppressed). It was noteworthy that Fe localization was clearly altered in nodule tissues of the knock-down line. These results strongly suggest that LjMATE1 is a nodule-specific transporter that assists the translocation of Fe from the root to nodules by providing citrate.

Evaluation of rotational instability in the anterior cruciate ligament deficient knee using triaxial accelerometer: a biomechanical model in porcine knees.

PURPOSE: To measure the acceleration in multiple directions of the rotational instability in ACL deficient models using porcine knees. METHODS: Ten porcine knees were tested with ACL intact and tear models. The pivot shift test was performed manually, and the acceleration of the pivot shift phenomenon was recorded by the use of a triaxial accelerometer. Tests were repeated in four different ACL states: (1) intact; (2) partial AM deficient; (3) complete AM deficient, and (4) complete ACL (AM and PL) deficient. The acceleration in three directions and the magnitude of acceleration were measured to evaluate rotational instability and compare between different ACL conditions. RESULTS: Significantly increased accelerations were observed in the complete deficient ACL model, while the partial ACL tear models demonstrated a slight increase without statistical significance. The accelerometer detected stepwise increases in the acceleration with the extent of ACL tear. Additionally, the PL bundle exhibited the largest contribution for rotational instability (80.4%) when compared with the AM (19.5%) bundles. CONCLUSION: Triaxial accelerometer could serve as a quantitative evaluation of rotational instability. The present study demonstrated that PL bundle has the most important contribution for rotational instability (80.4%) when compared to IM bundle (0.01%) and AM bundle (19.5%) in porcine knee model.

Crystal structures of human dipeptidyl peptidase IV in its apo and diprotin B-complexed forms.

Dipeptidyl peptidase IV (DPPIV), which belongs to the prolyl oligopeptidase family of serine proteases, is known to have a variety of regulatory biological functions and has been shown to be implicated in type 2 diabetes. It is therefore important to develop selective human DPPIV (hDPPIV) inhibitors. In this study, we determined the crystal structure of apo hDPPIV at 1.9 A resolution. Our high-resolution crystal structure of apo hDPPIV revealed the presence of sodium ion and glycerol molecules at the active site. In order to elucidate the hDPPIV binding mode and substrate specificity, we determined the crystal structure of hDPPIV-diprotin B (Val-Pro-Leu) complex at 2.1 A resolution, and clarified the difference in binding mode between diprotin B and diprotin A (Ile-Pro-Ile) into the active site of hDPPIV. Comparison between our crystal structures and the reported apo hDPPIV structures revealed that positively charged functional groups and conserved water molecules contributed to the interaction of ligands with hDPPIV. These results are useful for the design of potent hDPPIV inhibitors.

Characteristic biological activities of lipopolysaccharides from Sinorhizobium and Mesorhizobium.

The biological actions of lipopolysaccharides (LPSs) from Sinorhizobium meliloti, Mesorhizobium loti and Escherichia coli were compared. In biological activities including lethality, production of tumor necrosis factor (TNF)-alpha and nitric oxide (NO), adjuvant action and Limulus activity, LPS from S. meliloti exhibited stronger actions than LPS from M. loti, but had a weaker action than LPS from E. coli. On the other hand, M. loti LPS showed a higher activity to activate human complement than S. meliloti LPS. Further, there was a significant difference in polymyxin B binding between S. meliloti LPS and M. loti LPS, suggesting a difference in the lipid A structure. LPSs from S. meliloti and M. loti seem to exhibit characteristic biological actions that may be dependent on the difference in the lipid A structure.

Doxorubicin directly binds to the cardiac-type ryanodine receptor.

The clinical use of doxorubicin, an antineoplasmic agent, is limited by its extensive cardiotoxicity which is mediated by the mobilization of intracellular Ca2+ from SR. In order to elucidate the mechanism of Ca2+ release, we analyzed the binding sites of doxorubicin on rabbit cardiac SR (sarcoplasmic reticulum). One of the binding sites was identified as cardiac-type ryanodine receptor (RyR2) which was purified by immunoprecipitation from solubilized cardiac SR in the presence of DTT. Ligand blot analysis revealed the direct binding of doxorubicin to RyR2. The binding of doxorubicin to RyR2 was specific and displaced by caffeine. Both doxorubicin and caffeine enhanced [3H]-ryanodine binding to RyR2 in a Ca2+ dependent manner. These results suggest that there is a doxorubicin binding site on RyR2.