Inhibition of non-homologous end joining mitigates paclitaxel resistance resulting from mitotic slippage in non-small cell lung cancer.

Mitotic slippage, which enables cancer cells to bypass cell death by transitioning from mitosis to the G1 phase without undergoing normal cytokinesis, is one likely mechanism of paclitaxel (PTX) resistance. DNA double-strand breaks (DSBs) in the G1 phase are mainly repaired through non-homologous end joining (NHEJ). Therefore, inhibiting NHEJ could augment the PTX-induced cytotoxicity by impeding the repair of PTX-induced DSBs during the G1 phase following mitotic slippage. We aimed to evaluate the effects of NHEJ inhibition on mitotic slippage after PTX treatment in non-small cell lung cancer (NSCLC). H1299, A549, H1975, and H520 NSCLC cell lines were employed. In addition, A-196 and JQ1 were used as NHEJ inhibitors. H1299 cells were PTX-resistant and exhibited an increased frequency of mitotic slippage upon PTX treatment. NHEJ inhibitors significantly augmented the PTX-induced cytotoxicity, DSBs, and apoptosis in H1299 cells. The newly generated PTX-resistant cells were even more prone to mitotic slippage following PTX treatment and susceptible to the combined therapy. Docetaxel further demonstrated synergistic effects with the NHEJ inhibitor in PTX-resistant cells. NHEJ inhibition may overcome intrinsic or acquired PTX resistance resulting from mitotic slippage by synergistically increasing the cytotoxic effects of antimitotic drugs in NSCLC.

New potentiators of amphotericin B activity, shodoamides A to C produced by Pseudophialophora sp. BF-0158.

During our screening program for new potentiators of amphotericin B activity against Candida albicans, shodoamides A to C (1-3) were isolated from a culture broth of the fungus Pseudophialophora sp. BF-0158 fermented under shaking conditions. A known congener named shodoamide D (4) in this paper was obtained from a culture broth of the BF-0158 strain fermented under static conditions. The structures of 1-4 were assigned based on spectroscopic analyses, including NMR and MS, and were found to have a common N-(2´,3´,4´-trihydroxybutyl)-6-methyl-2,4-tetradecadienamide structure. Compounds 1-3 exhibited no antifungal activity, but they induced up to 32-fold increases in amphotericin B activity against C. albicans by a microdilution method.

Screening for nasal carriage of Staphylococcus aureus among patients scheduled to undergo orthopedic surgery: Incidence of surgical site infection by nasal carriage.

BACKGROUND: Staphylococcus aureus (S. aureus), including MRSA, is considered to be the leading cause of surgical site infection (SSI) after orthopedic surgery. We screened for nasal carriers of S. aureus among patients who were scheduled to undergo orthopedic surgery at our hospital to reveal the effect of nasal S. aureus carriage on SSI. Our study design clearly has the intent of finding S. aureus nasal carriage and eradicating MRSA when found, and this strategy is to verify whether it's effective for preventing orthopedic surgical infections. METHODS: Subjects were 4148 patients who underwent preoperative screening for nasal carrier and subsequently underwent orthopedic surgery during a 7-year period between April 2007 and March 2014. The incidence of SSI among patients who were operated in our department was investigated, and the rates were compared between patients with and without nasal carriage to reveal the effect of preoperative nasal carriage on SSI. RESULTS: In total, 1036 patients were nasal carriers of S. aureus (carriage rate, 25.0%), whereas 140 patients carried MRSA (carriage rate, 3.4%). SSI developed in 24 patients [incidence, 0.58% (24/4148)] consisting of 12 non-carriers [0.39% (12/3112)] and 12 carriers [1.16% (12/1036)] with a significant difference in the incidence between the groups. Among 24 cases of SSI, more than half (13 cases) were caused by bacterial species other than S. aureus or those that could not be detected by the tests used. Only 7 patients out of 24 SSI patients, S. aureus was the bacterium detected in preoperative nasal cultures and the causal bacterium for SSI (concordance rate of 29.2%). CONCLUSIONS: It was difficult to reduce the incidence rate of SSI in eradication group to the same level as nasal culture negative group. However, nasal carriage of S. aureus or MRSA may be a risk factor for SSI in orthopedic surgery.

Failure rates of Asian-type anatomic medullary locking stemmed metal-on-metal total hip replacement: A cause for adverse tissue reactions to metal debris (ARMD).

BACKGROUND: Adverse tissue reaction to metal debris (ARMD) as a secondary complication of Metal-on-metal total hip replacement (MoM THR) has been of concern. We have been performing cementless MoM THR using an Asian-type anatomic medullary locking (AML) stem. The purpose of this study is to examine the incident rate of ARMD, and the implant survival rate. METHODS: The study included 187 patients (211 hip joints) who underwent MoM THR between February 2007 and November 2009 at our hospital and who were followed up for a minimum of 6 years. The cases included 174 female joints and 37 male joints. The average age at the time of surgery was 68.4 years. The average postoperative follow-up period was 87.5 months. RESULTS: ARMD was observed in 23 joints postoperatively, and the incidence rate was 10.9%. Most of the instances occurred within the first 30 months postoperatively. Revision surgery was performed for 14 joints after conservative treatment failed, and we changed the bearing surface. During the intraoperative observation, black-colored deposition of metal debris on the head-neck junction was observed in 13 cases. Kaplan-Meier analysis using the replacement surgery as the end point showed that this implant has a survival rate of 93.8% 7 years after the primary surgery. CONCLUSIONS: We conclude that the major cause of failure of Asian-type AML stemmed MoM THR is likely the breakage of the fixation between the taper neck and metal head at the head-neck junction.

Chondrogenesis in the synovial tissue is associated with the onset of pseudogout after total knee arthroplasty.

Postoperative pseudogout after total knee arthroplasty (TKA) is very rare, and its physical findings are very similar to infectious symptoms. In pseudogout, the mechanism underlying the deposition of calcium pyrophosphate dehydrate crystals remains unclear. Here, we report the histologic findings in a pseudogout attack in the late postoperative period after TKA. She had acute onset of arthritis of the knee 2 years after TKA. Histologic examination showed significant neutrophil infiltration. Interestingly, chondrogenesis was noted in the synovial tissue, and calcium pyrophosphate dehydrate crystals were synthesized mainly at the site of chondrogenesis, suggesting a potential mechanism underlying the occurrence of pseudogout after TKA.

Pins and rubber band traction system and osteosynthesis with a hook plate for the treatment of old fracture-dislocation of a toe: application of hand operative techniques in a foot operation.

The treatment of old fracture-dislocation of a toe is usually difficult. The authors used 2 techniques that are commonly used in finger operations: One is the pins and rubber band traction system, and the other is the hook plate osteosynthesis. They treated a 56-year-old woman using these methods, and obtained a good result.

Diffuse arachnoid ossification and multiple arachnoid cysts presenting with progressive thoracic myelopathy.

An ossified arachnoid membrane combined with cystic formation is rarely reported as a cause of spinal cord compression. We report the case of a 60-year-old man who presented with diffuse ossification of the arachnoid membrane (arachnoid ossification) and multiple cystic changes (arachnoid cyst) at the thoracic and lumbar spine. The lesions were surgically removed and progressive deterioration was prevented, although no marked improvement of neurological symptoms was attained.

[A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy].

Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to take a malignant course. Most cases are young and early stage, and the surgical strategy is available. But appropriate chemotherapy for inoperable cases with peritoneal dissemination is not established. A 77-year-old woman with a past history of appendectomy was admitted to our hospital complaining of abdominal fullness. Abdominal computed tomography showed massive ascites and slight contrast enhancement of appendix. A tumor was found by colonoscopic examination at the orifice of vermiform and was diagnosed pathologically as goblet cell carcinoid of the appendix. Laparoscopy showed multiple peritoneal dissemination. We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week without any resection of the tumor. Ascites were reduced immediately, but drug-induced interstitial pneumonia occurred due to PTX. After steroid therapy, we switched to systemic S-1 therapy. For about one year, her tumor was controlled but became worse thirteen months after diagnosis and died. It is thought that intraabdominal paclitaxel administration and systemic S-1 therapy can be one of appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from goblet cell carcinoid of appendix.

Relationship between sex, age, and the minimum thickness of the roof of the glenoid fossa in normal temporomandibular joints.

This autopsy study investigates the minimum thickness of the roof of the glenoid fossa of grossly normal temporomandibular joints (TMJ) and correlates this to gender and age. This study was based on 49 TMJ specimens collected from 26 male and 23 female cadavers whose mean age at death was 73.8 years (range=50-96). No information was available about TMJ symptoms before death. A digital micrometer was used to measure the minimum thickness of the glenoid fossae. Comparisons were made based on gender and age. The mean value for the minimum roof thickness of all joint specimens examined was 0.8 mm. Mean values for male and female specimens were 0.8 and 0.7 mm, respectively, which were not significantly different. In addition, no age-related differences were observed. The average thickness was 0.7 mm for individuals in their fifties, 0.8 mm for those in their sixties and seventies, 0.6 mm for those in their eighties, and 0.8 mm for individuals in their nineties. Although these data indicate that the minimum thickness of the glenoid fossa of the TMJ is not significantly correlated with sex or age in patients 50 years of age and older, they nonetheless provide additional information about normal TMJ anatomy, particularly with regard to our knowledge of joint remodeling and function in the disease and non-disease states. Thickness of the glenoid fossa has also been implicated as a factor in facial trauma involving superior displacement of the mandibular condyle into the middle cranial fossa. The thickness of the glenoid fossa is also of potential interest during surgeries involving the glenoid fossa, such as TMJ arthroplasty or joint reconstruction.