<臨床>胃切除術後の単位体積当たりの骨密度の変化 : Dual energy X-ray absorptiometry (DXA) 法による検討

We used dual energy X-ray absorptiometry (DXA) to study changes in estimated volumetric bone mineral density (EstVBMD) of the lumbar spine after gastrectomy. The study group comprised 41 men and 32 women. When EstVBMD was compared according to sex among patients younger than 60 years of age, patients 60 to 69 years of age, and patients these three groups in men (0.185 g/cm_3, 0.187 g/cm_3, 0.187 g/cm_3, respectively). In contrast , EstVBMD was significantly lower in women 60 to 69 years of age (0.157 g/cm_3) and those 70 years of age or older (0.159 g/cm_3) than in women younger than 60 years (0.200 g/cm_3) (P<0.01). When the relation between EstVBMD and the number of months after gastrectomy was studied according to sex in patients younger than 70 years, EstVBMD negatively correlated with the interval after operation in men (r= -0.365, P<0.05), whereas ther e was no correlation between these variables in women. These results suggest that after gastrectomy bone mineral density decreases gradually in men younger than 70 years, but not in women. The lack of a consistent change in bone mineral density after gastrectomy in women is apparently caused by the marked effect on bone metabolism of decreased female hormone levels after menopause.胃切除後の腰椎の骨密度の変化を dual energy X-ray absorptiornetory （DXA） 法で測定し, 単位体積当たりの計測値（Estimated volumetric bone mineral density: EstVBMD）を求めることにより検討した. 男女別に60歳未満, 60歳代, 70歳以上の群で比較すると, 男性では 0.185 g/cm_3, 0.187 g/cm_3, 0.187 g/cm_3と大差がなかった. 一方, 女性では 0.200 g/cm_3, 0.157 g/cm_3, 0.159 g/cm_3 と60歳未満の症例と比較し60歳代, 70歳以上の症例では減少し有意差を認めた. 70歳未満の症例で男女別に術後月数と骨密度との関係をみると, 男性では経過期間とともに骨密度は減少し, 負の相関関係 （r= -0.365, P<0.05）が認められたが, 女性では両者は独立した関係であった. 70歳未満の男性では胃切術後に徐々に骨塩量が低下するが, 女性では閉経後の女性ホルモン減少が強く骨代謝に現れるため胃切術後の影響が個々で異なることが示唆された

A Proteomic Approach for Comprehensively Screening Substrates of Protein Kinases Such as Rho-Kinase

BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity

Clinicopathological Features and Outcomes of Endoscopic Submucosal Dissection for Superficial Cancer of the Pharynx

The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. “Resect and watch” is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer

Gain-of-function IKBKB mutation causes human combined immune deficiency

Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in two separate kindreds in whom probands presented with immune dysregulation, combined T and B cell deficiency, inflammation, and epithelial defects. IKBKB encodes IKK2, which activates NF-κB signaling. IKK2V203I results in enhanced NF-κB signaling, as well as T and B cell functional defects. IKK2V203 is a highly conserved residue, and to prove causation, we generated an accurate mouse model by introducing the precise orthologous codon change in Ikbkb using CRISPR/Cas9. Mice and humans carrying this missense mutation exhibit remarkably similar cellular and biochemical phenotypes. Accurate mouse models engineered by CRISPR/Cas9 can help characterize novel syndromes arising from de novo germline mutations and yield insight into pathogenesis

<原著>高齢者急性胆囊炎症例の臨床的検討

In recent years, an increase in average life expectancy has led to a rapid rise in the number of elderly patients undergoing surgeηr for acute cholecystitis. We studied the clinical characteristics of elderly patients (aged 7S years of more） undergoing surgery for acute cholecystitis, as compared with those of non-elderly patients (aged less than 75 years) undergoing similar procedures. Twenty-four of the patients were elderly, and 44 were non-elderly. [Results J Echography and abdominal computed tomography (CT) revealed no characteristic findings specific to elderly patients, but a smaller proportion of elderly patients showed a three-layered structure of the gallbladder wall. The leukocyte count on admission was significantly lower in elderly patients than in non-elderly patients. As for therapy, a significantly higher proportion of elderly patients underwent percutaneous transhepatic gallbladder drainage (PTG BD) + cholecystectomy+ choledochotomy/choledocholithotomy, as compared with non-elderly patients. In contrast, cholecystectomy alone was performed more frequently in non-elderly patients than in elderly patients. The main postoperative complications were psychic symptoms and respiratory tract infections. The postoperative hospital stay was significantly longer for elderly patients, in part because they requested to remain in the hospital until they were able to perform activities of daily living.[要旨]近年, 平均寿命の延長に伴い, 高齢者の急性胆嚢炎手術例も急増してきた. 高齢（75歳以上）と非高齢者（75歳未満）を比較し, 高齢者の急性胆嚢炎手術症例について臨床的特徴を検討した. 1989年4月より6年聞に急性胆嚢炎として手術した症例は68例であった. 高齢者は24例で, 非高齢者は44例であった. [成績] echo像, 腹部CT検査所見では, 特徴的な所見は得られなかったが, 壁の三層構造を示す症例が少なかった. 入院時の白血球数は非高齢者より有意に少なかった. 治療法では胆摘のみの症例よりもPTGBD＋胆摘＋総胆管切開術の症例が有意に多かった. 術後合併症では精神症状や呼吸器感染が多く認められた. また, 壊疽性胆嚢炎に胆嚢穿孔と胆汁性腹膜炎併発し, 術後多臓器不全で死亡した症例以外は前例救命しえた. 在院日数は日常生活が出来るまで在院させてほしいとの希望もあり有意に長かった

<臨床>Microdensitometory 法と dual energy X-ray absorptiometory 法を用いた胃切除術後骨障害の検討

We used microdensitometry (MD) and dual energy X-ray absorptiometry (DXA) to evaluate impaired bone metabolism in 79 patients who had undergone gastrectomy. With MD, radiographs are simultaneously taken of the second metacarpal bone and an aluminum step-wedge, and the images were analyzed by computer. DXA was used to measure the bone mineral density of the second through fourth vertebrae and the estimated volumetoric bone mineral density (EstVBMD) was assessed . Significant positive correlations were obtained between EstVBMD as determined by DXA and metacarpal index (MCI) (r=0.413, P<0.01), peak of the cortex (GSmax) (r=0.362, P<0.05), peak of the middle portion of the bone marrow (GSmin) (r=0.412, P<0.01), and metacarpal bone mineral density (mBMD) (r=0.413, P<0.01) as determined by MD. When EstVBMD was compared with MCI, GSmax, GSmin, and mBMD according to sex, age, type of operation, and interval after operation, generally similar trends were obtained. We conclude that the determination by MD of various indices of bone metabolism is useful in the diagnosis of osteopathy after gastrectomy