Co-existence of inhibitory and stimulatory factors modulating cell proliferation in rat liver cytoplasm.

Factors that inhibit and stimulate cell proliferation were found to coexist in rat liver supernatant. The inhibitory and stimulatory factors were separated by ethanol fractionation. Both factors were sensitive to heat- and trypsin-treatment. The activity of the inhibitor was diminished by partial hepatectomy. The inhibitor from normal livers inhibited DNA and RNA synthesis in the L-cell system, but the same fraction from regenerating livers caused little or no inhibition of nucleic acid synthesis. The stimulatory factor from regenerating livers had a stronger effect on cell proliferation than that of normal livers. Furthermore, the inhibitor from normal livers depressed DNA synthesis in vivo in regenerating livers

Increased intrapharyngeal pressure with combined use of high-flow nasal cannula and a surgical face mask: a preliminary study

OBJECTIVES: Nasal high-flow (NHF) therapy provides continuous positive airway pressure (CPAP), flushes the anatomical dead space, and improves mucociliary clearance. CPAP is usually applied at a flow rate at or above an established threshold value with the mouth closed because it is hard to maintain it with an open mouth. We conducted a prospective study to validate our hypothesis that CPAP can be applied with the mouth open through a surgical face mask. METHODS: We inserted 12-Fr nasogastric tubes through the noses of 18 healthy individuals and fixed each tube within the pharynx to monitor the intrapharyngeal pressure. We monitored the pressure during the following two conditions: NHF oxygen with the mouth open (condition O) and NHF oxygen with the mouth open and wearing a surgical face mask (condition OM). We set the NHF rate at 40 L/min and the oxygen concentration at 21%, under all conditions. We measured the intrapharyngeal pressure five times during each inspiration and expiration, and calculated mean values. RESULTS: The mean expiratory intrapharyngeal pressure (median [interquartile range]) increased significantly from the baseline during conditions O (2.08 [1.58–4.02] cm H(2)O) and OM (3.35 [2.72–3.79] cm H(2)O). In addition, there was a significant difference in pressure between conditions O and OM (p=0.0263, Wilcoxon signed-rank test). CONCLUSIONS: In our healthy volunteers, the intrapharyngeal pressures increased during expiration with an open mouth while wearing a surgical face mask

Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts

Background: Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36γ using human colonic subepithelial myofibroblasts (SEMFs). Methods: The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-κB p65. Results: IL-36α and IL-36γ significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36α/γ and IL-17A or of IL-36α/γ and tumor necrosis factor (TNF)-α showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36α and/or IL-36γ was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases (MAPKs) and siRNAs specific for NF-κBp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36α and/or IL-36γ. Conclusion: These results suggest that IL-36α and IL-36γ contribute to gut inflammation through the induction of proinflammatory mediators

Multiplex cDNA quantification method that facilitates the standardization of gene expression data

Microarray-based gene expression measurement is one of the major methods for transcriptome analysis. However, current microarray data are substantially affected by microarray platforms and RNA references because of the microarray method can provide merely the relative amounts of gene expression levels. Therefore, valid comparisons of the microarray data require standardized platforms, internal and/or external controls and complicated normalizations. These requirements impose limitations on the extensive comparison of gene expression data. Here, we report an effective approach to removing the unfavorable limitations by measuring the absolute amounts of gene expression levels on common DNA microarrays. We have developed a multiplex cDNA quantification method called GEP-DEAN (Gene expression profiling by DCN-encoding-based analysis). The method was validated by using chemically synthesized DNA strands of known quantities and cDNA samples prepared from mouse liver, demonstrating that the absolute amounts of cDNA strands were successfully measured with a sensitivity of 18 zmol in a highly multiplexed manner in 7 h

Impact of patient characteristics on the efficacy and safety of landiolol in patients with sepsis-related tachyarrhythmia: Subanalysis of the J-Land 3S randomised controlled study

Background The J-Land 3S trial demonstrated that landiolol is effective and tolerated for treating sepsis-related tachyarrhythmias. Patient characteristics (e.g. baseline heart rate [HR], type of tachyarrhythmia, and concomitant disorders) may impact the outcomes of landiolol therapy. We performed subanalyses of J-Land 3S to evaluate the impact of patient characteristics on the efficacy and safety of landiolol for treating sepsis-related tachyarrhythmia. Methods Patients (≥20 years old; N = 151) hospitalised with sepsis at 54 participating hospitals in Japan with HR ≥100 beats/min for ≥10 min accompanied by diagnosis of tachyarrhythmia were randomised 1:1 to conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group). The efficacy and safety of landiolol were assessed in prespecified analyses of patients divided into subgroups by baseline characteristics and in post hoc, multivariate analyses with adjustment for age and HR at baseline. Findings The percentage of patients with HR of 60–94 beats/min at 24 h after randomisation (primary endpoint) was greater in the landiolol group in most subgroups in univariate unadjusted analyses and in multivariate logistic regression. The incidence of new-onset arrhythmia by 168 h and mortality by 28 days were also lower in the landiolol group in most subgroups in univariate and multivariate Cox proportional hazards models. No subgroups showed a markedly higher incidence of adverse events in univariate or multivariate logistic regression analyses

<症例>胃癌手術 (脾摘術合併胃全摘術) 後の門脈血栓症の1例

A 48-year-old woman underwent total gastrectomy, splenectomy, and distal pancreatectomy with en bloc regional lymph node dissection for gastric carcinoma. Dull pain in the right upper quadrant and the back developed postoperatively. Contrast-enhanced computed tomography and ultrasonography disclosed portal vein thrombosis (PVT). Heparin and urokinase were given in conjunction with antbiotics. This treatment resulted in clinical improvement, but failed to achieve complete thrombolysis. Cavernous transformation of the portal system was confirmed. Although PVT after splenectomy has been reported mainly in patients with hematological disorders, our case suggests that splenectomy for en bloc node dissection in gastric carcinoma is a possible cause of PVT.門脈血栓症は肝硬変や肝癌の患者で時に認められる病態であるが, 術後の門脈血栓症は稀であり, そのほとんどが脾腫に対する脾摘術後に発生している. 我々は胃癌根治術に伴う脾摘術後に門脈血栓をきたした症例を経験したので報告する. 症例は48才の女性で, 胃体上部後壁を中心とする5型胃癌に対し, 胃全摘術, 脾摘術, 膵尾側切除術を行なった. 病変は組織学的には低分化腺癌, 深達度ss, No, Po, Ho の stage I b で, 摘出した脾重量は 150g であった. なお, 術前の出血凝固系検査には異常を認めなかった. 術後18日目より右上腹部から背部の鈍痛が出現し, 白血球数, CRP, 血清アルカリフォスファターゼ値も上昇してきた. 術後19日目の造影CTで, 門脈, 上腸間膜静脈がほとんど造影されず, 門脈から上腸間膜静脈におよぶ血栓形成が考えられた. 抗生剤の投与とともにただちにへパリンの持続静注とウロキナーゼ投与を併用したところ, 臨床症状や検査所見は軽快した. ただし, 血栓は完全に消失せず, その後の腹部血管造影では側副血行路としての肝十二指腸間膜内の静脈拡張, いわゆるcavernous transformation が認められた. へパリン, ウロキナーゼの投与からワーファリン内服に切り替え, 患者は術後66日目に退院した. 現在, 術後2年経過したが, 食道静脈瘤の出現や消化管出血などの門脈血栓, 門脈圧充亢進に起因すると思われる症状は認めていない. 我々の症例は, 進行胃癌根治術の際にしばしは合わせ行われる脾摘術後にも門脈血栓症の出現する可能性があることを示唆しており, そのような手術を受けた患者が術後原因不明の腹部症状や白血球増加を来たした時には門脈血栓症も疑い精査を進める必要があると考えられる