Differences in specificities of anti-centromere sera for the monomeric and dimeric C-terminal peptides of human centoromere protein C

Centromere protein-C (CENP-C), one of the centromere autoantigens and components of the inner plate of the kinetochore, is suggested to make a dimer at the C-terminus. In order to investigate the presence of conformation-specific anti-centromere antibodies (ACA) to the dimer form, the C-terminal 124 amino acids (CF-124) were expressed in Escherichia coli, affinity purified and chemically cross-linked. Immunoblotting was utilized to compare the reactivities between the dimers and the monomers against 58 ACA(+) sera. The reactivities of the dimers were obviously higher in both IgG and IgM responses. The dimer was still more reactive than the glutathione S-transferase-fused monomer in some sera. Two kinds of CF-124 mutant (each contained one amino acid change at the N-terminal region of CF-124) and two cut segments of CF-124 (67 N-terminal amino acids and 58 C-terminal amino acids) were also examined. The former two mutants decreased the dimerization activity. The latter two mutants lost both activities except for the faint dimerization activity of the N-terminal half. Affinity-purified antibodies with CF-124 in a liquid phase containing the co-purified GroE protein of E. coli, GroEL, reacted to the centromere in culture cells. In conclusion, there are heterogeneous autoepitopes including some conformational epitopes at the C-terminal CENP-C.     

Posterior Ankle Decompression With Os Trigonum or Stieda Process Resection in Dancers: Case Series Report and Review of the Literature

This case series reports the outcome of posterior ankle decompression and os trigonum or Stieda process resection utilizing an open posterolateral approach in 54 professional, pre-professional, and dedicated recreational dancers. All procedures were performed by a single surgeon at the same facility between 2008 and 2018. The surgical technique is described in detail. Data related to results of the surgery were gathered via follow-up questionnaire and verified by referencing the patients’ medical records. Outcomes were self-assessed in terms of categories ranging from excellent through moderate to poor. Eighty-nine percent of the dancers (N = 48 of 54) chose excellent or good, 11% (N = 6) chose moderate, and none selected poor. These results were compared with those achieved in 17 previous studies reporting the use of both open (posterolateral and posteromedial) and arthroscopic/endoscopic techniques in dancers. This comparison found similarly favorable reported outcomes, but also great variation in methodology for determining patient reported outcomes (PROs). While the preferred surgical technique for posterior ankle decompression remains controversial, the open posterolateral approach utilized in this series resulted in high expectation of return to dance with minimal complications. The need for a dancer-specific PRO tool is discussed.     

Alcohol intake in early adulthood and risk of colorectal cancer: three large prospective cohort studies of men and women in the United States

European Journal of Epidemiology - Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association...     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Clinical significances of intraoperative radiation therapy for aged patients with bladder cancer]

Seven elderly patients, 79-88 years old, with bladder cancer were treated by transvesical tumorectomy with intraoperative radiation therapy (IORT). The cancers appeared to be of high grade and high stage by cystoscopy and other examinations, and consequently they were diagnosed to be over stage T2. Therefore, all patients were thought to be candidates for total cystectomy. But their ages and complications precluded this treatment, so we decided to carry out the "palliative" IORT. The operation of IORT required less than two hours and required less than 200 ml of blood loss. There were no complications such as hematuria, irritable bladder, and rectal symptoms. The postoperative stage diagnoses coincided with the preoperative ones in 5 cases, but two cases were overdiagnosed. Five patients died after more than one year and 11 months, but four patients died due to other diseases, without cancer. One patient died due to pulmonary cancer confirmed by autopsy. Recurrence was seen in one case. These results confirmed that IORT was effective for local control of bladder cancer and partially prophylactic for recurrence. Furthermore, this treatment seemed to be even curative for some cases. We recommend this modality of treatment for some of aged patients and patients with complications who are unable to undergo cystectomy.     

Immunohistochemical detection of P-glycoprotein in breast cancer and its significance as a prognostic factor

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35 (37.2%) were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary lymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p = 0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p = 0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.     

Enhancement of sensitivity to CDDP in human pharyngeal carcinoma cells by H-7, a protein kinase inhibitor

We investigated the synergetic effects of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) on cis-diamminedichloroplatinum(II) (CDDP) cytotoxicity to KB cells, a human pharyngeal carcinoma cell line, and explored the possible mechanism whereby it exerted these effects. In vitro treatment with H-7 markedly decreased protein kinase C (PKC) activity in KB cells and significantly sensitized the cells to CDDP. Treatment of KB cells with H-7 induced a dose-dependent depletion of intracellular glutathione (GSH) levels. These results suggest that the decreased GSH content induced by H-7 may be involved in sensitizing KB cells to CDDP.     

Coronary artery bypass grafting in two patients with single coronary artery

We experienced two patients with single coronary artery who underwent CABG using arterial grafts successfully. In two patients coronary angiography demonstrated a single coronary artery which was originated in left coronary sinus and was bifurcated to LAD and LCx, and then RCA branched off proximal LAD, passing in front of the right ventricular out flow tract (Sharbaugh Type L-IIa). To the first patient, a 52-year-old man who had angina on exertion due to long stenosis of RCA, CABG to RCA using RITA was carried out. To the second patient, a 57-year-old man who had inferior myocardial infarction due to 90% stenosis of proximal LAD, CABG to RCA using RITA and LAD using LITA was carried out. Single coronary artery without additional congenital cardiac anomalies may lead to myocardial ischemia, necessitating CABG as coronary reconstructions.