α1-Syntrophin–deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration

α1-Syntrophin is a member of the family of dystrophin-associated proteins; it has been shown to recruit neuronal nitric oxide synthase and the water channel aquaporin-4 to the sarcolemma by its PSD-95/SAP-90, Discs-large, ZO-1 homologous domain. To examine the role of α1-syntrophin in muscle regeneration, we injected cardiotoxin into the tibialis anterior muscles of α1-syntrophin–null (α1syn−/−) mice. After the treatment, α1syn−/− muscles displayed remarkable hypertrophy and extensive fiber splitting compared with wild-type regenerating muscles, although the untreated muscles of the mutant mice showed no gross histological change. In the hypertrophied muscles of the mutant mice, the level of insulin-like growth factor-1 transcripts was highly elevated. Interestingly, in an early stage of the regeneration process, α1syn−/− mice showed remarkably deranged neuromuscular junctions (NMJs), accompanied by impaired ability to exercise. The contractile forces were reduced in α1syn−/− regenerating muscles. Our results suggest that the lack of α1-syntrophin might be responsible in part for the muscle hypertrophy, abnormal synapse formation at NMJs, and reduced force generation during regeneration of dystrophin-deficient muscle, all of which are typically observed in the early stages of Duchenne muscular dystrophy patients

A case of multiple pancreatic cysts with K-ras point mutation in pure pancreatic juice

膵癌の早期診断を行うために,最近の進歩の著しい遺伝子診断を用いて,膵液中のK-ras遺伝子の点突然変異の検討がなされている｡われわれは膵液の細胞診は陰性であるが,K-ras遺伝子の点突然変異を認め,膵全体に多発する膵嚢胞の1例を経験した｡本例は悪性であるとの確診が得られないことや切除するとなれば膵全摘となることなどのために,経過観察を行っているが,18カ月後の現在,嚢胞の増大など認めていない｡膵癌の遺伝子診断の文献的考察を含め,報告する｡Pancreatic cancer is the one of the leading causes of death among cancer deaths and the early diagnosis is one of the main topics of pancreatic research. Mutation of K-ras oncogene at codon 12 has been reported in pancreatic adenoma, hyperplasia of the pancreatic duct, and also in pancreatic cancer, Recently, detection of K-ras point mutation in pure pancreatic juice is underinvestigation as a potential tool of early diagnosis of pancreatic cancer by setting a certain cut-off value. We recently experienced a case of multiple pancreatic cysts without any malignant cells in pancreatic juice, but with a positve point mutation of K-ras oncogene. Operation was deferred after obtaining informed consent from the family, because the lesions were so multiple and extensive as to require total pancreatectomy. Eighteen months follow-up studies did not reveal any deterioration in imaging tests as well as clinical picture

Gastro-biliary motility in patients with non-ulcer dyspepsia

現在,上腹部不定愁訴の原因は特定されていない｡その原因を解明するため,上腹部不定愁訴患者8人と健常対照者10人に対して液体食の胃排出能と,食事負荷による胆嚢収縮能を測定した｡胃排出時間,胆嚢収縮能はいずれも両者に有意な差は認められなかった｡健常対照者では胃排出時間と胆嚢収縮時間に有意な相関関係が認められたが,上腹部不定愁訴群では相関関係は認められなかった｡上腹部不定愁訴の原因として胃･胆嚢協調運動障害の存在が示唆 された。Subjective symptoms are quite similar between cystic duct syndrome (CDS) and non-ulcer dyspepsia (NUD) : epigastralgia, hypochondralgia and vague complaints in the upper part of the abdomen. Recently, there has been several reports suggesting that the cause of these disorders is postprandial dysmotility in the gallbladder and stomach. However, there has been no report suggesting incoordination of postprandial gastrobilialy motility as the cause of tha above mentioned complaints in these disorders. The aim of this study was to define the difference of postprandial gastrobiliary motility between patients with NUD and controls. Eight patients with NUD and 10 controls were studied. Gastric emptying time of liquid meal and gallbladder contraction were measured, simultaneously. There was no significant difference between study patients and controls when gastric emptying time and gallbladder contraction rate were compared in isolation. However, when these two parameters were assessed in combination, gastric emptying time was linearly correlated with minimum ballbladder contraction time in controls but not in patients. We conclude that the incoordination between gastric emptying and minimal gallbladder contraction may be one of the major causes of the symptoms in NUD

Mechanisms of pancreatic fibrosis

膵の線維化は慢性膵炎に特徴的な病理組織所見の一つであるが,その発生機序については不明な点か多い｡慢性膵炎はいったん発症すれば,進行性かつ非可逆性であるとされるが,その非可逆性に膵の線維化が関与するとされる｡膵の線維化の発生機序を明らかにし,線維化に対する根本的な治療法の確立が望まれるところである｡そこで,本稿では今後の膵の線維化の研究課題を明らかにする目的で,現在までの膵臓線維化の発生機序に関する知見を整理した｡Pancreatic fibrosis is an outstanding morphological feature in chronic pancreatis although it is seen in pancreatic cancer and convalescent stage of acute pancreatitis. Progressive fibrosis in chronic pancreatitis leads to the destruction and contributes to irreversiblity of chronic pancreatitis. Exact mechanisms of pancreatic fibrosis is not yet unclear, although advances in molecular biology have revealed possible roles of cytokines and growth factors in it. We summarized our understanding of pancreatic fibrosis in the revIew

Usefulness of retinol binding protein as a marker for the assessment of nutritional uptake for the preparation of colonosocpy

大腸内視鏡検査の前処置を栄養面から評価する目的で前処置前後にrapid turnover proteinである血中レチノール結合蛋白の変動を検討した｡前日に普通食を用い,当日ニフレックを使用した10例,検査1日前に低残渣食を用いた27例,通常の前処置では良好な腸管洗浄が得られないために検査前2日間低残渣食を用いた27例の3群について,前処置開始前と検査終了後に血中レチノール結合蛋白の変動をみたところ,検査前2日間低残渣食服用群で有意の低下を認めた｡前日普通食群では検査前後で変化を認めず,1日低残渣食服用群では低下傾向を認めたが,有意差は認めなかった｡これまで前処置の成否は腸管洗浄度の面で評価されてきたが,血中レチノール結合蛋白を目標として用いることにより栄養面から評価することができることが考えられた。The objective of this study was to evaluate the usefulness of retinol binding protein (RBP), one of rapid turnover proteins, for the assessment of nutritional aspect of the preparation for colonoscopy. Blood samples were drawed before the preparation and after the colonoscopic examination and serum RBP was determined by laser nephrometory. Group A consisted of 10 patients who were administered intestinal lavage solution (Niflec) without no low residual diet. Group B consisted of 27 patients who were adminstered low residual diet for 1 day. Group C consisted of 27 patients who were administered low residual diet for the two consecutive days before colonosocopic examination with intestinal lavage solution and magnesium citrate because sufficient cleanup of intestine were not expected by using the ordinary preparations. The values of serum RBP significantly decreased in group C after the preparation although no significant changes were observed in group A and Group B. We emphasized in estimating the preparation for the colonoscopy assessment of nutrition using serum RBP was needed as well as colonic cleaning

A comprehensive analysis of the correlations between resting-state oscillations in multiple-frequency bands and big five traits

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz) and slow-2 (0.198–0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females

Early-phase changes of extravascular lung water index as a prognostic indicator in acute respiratory distress syndrome patients

Background: The features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality. Methods: This was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated. Results: We evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. ?0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ? 2.8 (log-rank test, χ2 = 7.08, p = 0.008). Conclusions: Decrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required