GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation

AbstractWe identified two novel GATA2 mutations in acute myeloid leukemia (AML). One mutation (p.R308P-GATA2) was a R308P substitution within the zinc finger (ZF)-1 domain, and the other (p.A350_N351ins8-GATA2) was an eight-amino-acid insertion between A350 and N351 residues within the ZF-2 domain. p.R308P-GATA2 did not affect DNA-binding and transcriptional activities, while p.A350_N351ins8-GATA2 reduced them, and impaired G-CSF-induced granulocytic differentiation of 32D cells. Although p.A350_N351ins8-GATA2 did not show a dominant-negative effect over wild-type (Wt)–GATA2 by the reporter assay, it might be involved in the pathophysiology of AML by impairing myeloid differentiation because of little Wt-GATA2 expression in primary AML cells harboring the p.A350_N351ins8 mutation

前立腺導管癌の1例 : 通常型腺癌とは区別する臨床的意義に関する考察

根治的前立腺全摘除術を施行した前立腺導管癌の1例を報告する。病理学的病期(pT3bN1)は術前の臨床パラメータ(cT1cN0, PSA7.64ng/ml)に基づく予測よりも進行していた。主病変の導管型腺癌は移行領域を占拠し, その周囲に通常型腺癌の小病変が散在していた。また導管型腺癌細胞と通常型腺癌細胞とが隣接して同一腺管の中に共存する部位も認められた。リンパ節転移部位には導管型腺癌細胞のみが認められた。さらに両型の腺癌細胞においてPSA蛋白の強発現とp63蛋白の消失がみられることを免疫組織化学的に確認した。前立腺導管癌を通常型腺癌と区別する臨床的意義について考察した。(著者抄録)We report a case of prostatic duct adenocarcinoma treated with radical prostatectomy. Advanced pathological stage (pT3bpN1) was beyond the prediction of the favorable preoperative parameters (cT1cN0, PSA 7.64 ng/ml). The main tumor of ductal adenocarcinoma was occupying the transitional zone and surrounded by scattered micro-foci of acinar adenocarcinoma. We identified coexistence of ductal and acinar adenocarcinoma cells side by side in the same gland. Pure ductal cancer cells were detected in the metastasized lymph node without acinar cancer cells. Strong staining of PSA and loss of p63 expression by both types of adenocarcinoma cells were confirmed immunohistochemically. We discuss the clinical significance of prostatic duct adenocarcinoma in comparision with typical acinar adenocarcinoma

A comparison of sex- and weight-based ProsSeal laryngeal mask size selection criteria: a randomized study of healthy anesthetized, paralyzed adult patients

Background: The authors compared the manufacturer's weight-based formula (size 3 for weight < 50 kg, size 4 for weight 50-70 kg, and size 5 for weight > 70 kg) with a sex-based formula (size 4 for women and size 5 for men) for selecting the appropriate size of ProSeal™ laryngeal mask airway.\ud \ud Methods: Two hundred thirty-seven healthy, anesthetized, paralyzed adult patients (American Society of Anesthesiologists physical status I or II; age, 18-80 yr) were randomly allocated for weight- or sex-based size selection. An experienced user inserted the ProSeal™ laryngeal mask airway with the digital technique. The following were compared: ease of insertion, oropharyngeal leak pressure, ease of ventilation, gas exchange, location of gas leak, anatomic position, mucosal injury, and postoperative pharyngolaryngeal problems. Intraoperative and postoperative data collection were unblinded and blinded, respectively.\ud \ud Results: Ease of insertion, anatomic position, gas exchange, mucosal injury, and postoperative pharyngolaryngeal problems were similar between groups. For the sex-based group, larger ProSeal™ laryngeal mask airways were selected more frequently (P < 0.0001), oropharyngeal leak pressure (P = 0.02) was higher, leak volume (P = 0.004) and leak fraction (P = 0.007) were lower, and oropharyngeal leaks (P = 0.03) were detected less frequently.\ud \ud Conclusion: Size selection for the ProSeal™ laryngeal mask airway is equally effective using the manufacturer's weight-based formula or the sex-based formula in healthy, anesthetized, paralyzed adult patients, but leakage of small volumes of air from the mouth occurs less frequently with the sex-based formula.\u

Influence of nitrous oxide on minimum alveolar concentration of sevoflurance for laryngeal mask insertion in children

Background: Inhalational induction with sevoflurane and nitrous oxide is frequently used for Laryngeal Mask Airway ™ (LMA ™; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) insertion in children. The authors determined the influence of nitrous oxide on the minimum alveolar concentration (MAC) of sevoflurane for LMA ™ insertion.\ud \ud Methods: One hundred twenty unpremedicated children (age, 1-9 yr; American Society of Anesthesiologists physical status I) were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0, 1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or 1.2% sevoflurane. The LMA ™ was inserted after steady state end-tidal anesthetic concentrations had been maintained for 15 min. The response to insertion was recorded by three independent blinded observers. The interaction between nitrous oxide and sevoflurane was determined using logistic regression analysis.\ud \ud Results: The MAC of sevoflurane for LMA ™ insertion (95% confidence limit) was 1.57% (1.42-1.72%), and the concentration of sevoflurane required to prevent movement in 95% of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide linearly decreased the MAC of sevoflurane for LMA ™ insertion by 22% and 49%, respectively (P < 0.001). The interaction coefficient between nitrous oxide and sevoflurane did not differ from zero (P = 0.7843), indicating that the relation was additive.\ud \ud Conclusions: Nitrous oxide and sevoflurane suppress the responses to LMA ™ insertion in a linear and additive fashion in children.\u

Influence of Nitrous Oxide on Minimum Alveolar Concentration of Sevoflurane for Laryngeal Mask Insertion in Children

Background: Inhalational induction with sevoflurane and nitrous oxide is frequently used for Laryngeal Mask Airway™ (LMA™; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) insertion in children. The authors determined the influence of nitrous oxide on the minimum alveolar concentration (MAC) of sevoflurane for LMA™ insertion. Methods: One hundred twenty unpremedicated children (age, 1-9 yr; American Society of Anesthesiologists physical status I) were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0, 1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or 1.2% sevoflurane. The LMA™ was inserted after steady state end-tidal anesthetic concentrations had been maintained for 15 min. The response to insertion was recorded by three independent blinded observers. The interaction between nitrous oxide and sevoflurane was determined using logistic regression analysis. Results: The MAC of sevoflurane for LMA™ insertion (95% confidence limit) was 1.57% (1.42-1.72%), and the concentration of sevoflurane required to prevent movement in 95% of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide linearly decreased the MAC of sevoflurane for LMA™ insertion by 22% and 49%, respectively (P < 0.001). The interaction coefficient between nitrous oxide and sevoflurane did not differ from zero (P = 0.7843), indicating that the relation was additive. Conclusions: Nitrous oxide and sevoflurane suppress the responses to LMA™ insertion in a linear and additive fashion in children

Carbon-ion beam irradiation effectively suppresses migration and invasion of human non-small-cell lung cancer cells

PURPOSE: Control of cancer metastasis is one of the most important issues in cancer treatment. We previously demonstrated that carbon particle irradiation suppresses the metastatic potential of cancer cells, and many studies have reported that photon irradiation promotes it. The purpose of this study was to investigate the effect of carbon beam on non-small-cell lung cancer (NSCLC) cell aggressiveness and gene expression. METHODS AND MATERIALS: A549 (lung adenocarcinoma) and EBC-1 (lung squamous cell carcinoma) cells were treated with 290 MeV/nucleon carbon ion beam at the Heavy Ion Medical Accelerator in Chiba or with 4-MV X-ray at Osaka University. We tested proliferative, migratory, and invasive activities by cell proliferation assay, Boyden chamber assay, and Matrigel chemoinvasion assay, respectively. cDNA microarray and reverse transcription polymerase chain reaction were also performed to assess mRNA expression alteration. RESULTS: X-irradiation increased cell proliferation of A549 cells at 0.5 Gy, whereas high-dose X-ray reduced migration and invasion of A549 cells. By contrast, carbon beam irradiation did not enhance proliferation, and it reduced the migration and invasion capabilities of both A549 and EBC-1 cells more effectively than did X-irradiation. Carbon beam irradiation induced alteration of various gene expression profiles differently from X-ray irradiation. mRNA expression of ANLN, a homologue of anillin, was suppressed to 60% levels of basal expression in carbon beam-irradiated A549 cells after 12 h. CONCLUSION: Carbon beam effectively suppresses the metastatic potential of A549 and EBC-1 cells. Carbon beam also has different effects on gene expressions, and downregulation of ANLN was induced only by carbon beam irradiation