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Coarse-graining of perplexity for the spatial distribution of molecules
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Biological tissue consists of various molecules. Instead of focusing on a particular molecule, we consider the Shannon entropy which is calculated from the abundance of different molecules at each spot in the tissue. The spatial distribution of the Shannon entropy is of interest. In this paper, we first obtain the heat map of perplexity, whose logarithm is the entropy. To characterize the spatial variety of molecules, we propose a scalar k that is concerned with the coarse-graining of the perplexity heat map. To verify the usefulness of the number, experiments with mass spectrometry imaging were performed for mouse kidneys. We found that k has large values in the renal pelvis area, cortex area, veins, and arteries in the mouse kidney, whereas fractal dimensions fail to distinguish those regions
Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Background & aims: Liver fibrosis characterizes advanced chronic liver disease, and persistent activation of hepatic stellate cells (HSCs) is the primary cause of excessive hepatic fibrogenesis. CWHM12, an analog of the arginine-glycine-aspartic acid (RGD) amino acid sequence found in specific integrins, improves liver fibrosis; however, the detailed mechanisms remain unclear. This study aimed to clarify the cell signaling mechanisms of CWHM12 in activated HSCs.
Methods: Immortalized human HSC lines, LX-2 and TWNT-1, were used to evaluate the effects of CWHM12 on intracellular signaling via the disruption of RGD-binding integrins.
Results: CWHM12 strongly promoted phosphorylation and inhibited the nuclear accumulation of Yes-associated protein (YAP), which is a critical effector of the Hippo signaling pathway, leading to the inhibition of proliferation, suppression of viability, promotion of apoptosis, and induction of cell cycle arrest at the G1 phase in activated HSCs. Further investigations revealed that inhibition of TGF-β was involved in the consequences of CWHM12. Moreover, CWHM12 suppressed focal adhesion kinase (FAK) phosphorylation; consequently, Src, phosphatidylinositol 3-kinase, pyruvate dehydrogenase kinase 1, and serine-threonine kinase phosphorylation led to the translocation of YAP. These favorable effects of CWHM12 on activated HSCs were reversed by inhibiting FAK.
Conclusions: These results indicate that pharmacological inhibition of RGD-binding integrins suppresses activated HSCs by blocking the Hippo signaling pathway, a cellular response which may be valuable in the treatment of hepatic fibrosis
Endocannabinoid 2-arachidonoylglycerol levels in the anterior cingulate cortex, caudate putamen, nucleus accumbens, and piriform cortex were upregulated by chronic restraint stress
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Endocannabinoid 2-arachidonoylglycerol (2-AG) has been implicated in habituation to stress, and its augmentation reduces stress-induced anxiety-like behavior. Chronic restraint stress (CRS) changes the 2-AG levels in some gross brain areas, such as the forebrain. However, the detailed spatial distribution of 2-AG and its changes by CRS in stress processing-related anatomical structures such as the anterior cingulate cortex (ACC), caudate putamen (CP), nucleus accumbens (NAc), and piriform cortex (PIR) are still unclear. In this study, mice were restrained for 30 min in a 50 mL-centrifuge tube for eight consecutive days, followed by imaging of the coronal brain sections of control and stressed mice using desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The results showed that from the forebrain to the cerebellum, 2-AG levels were highest in the hypothalamus and lowest in the hippocampal region. 2-AG levels were significantly (p<0.05) upregulated and 2-AG precursors levels were significantly (p<0.05) downregulated in the ACC, CP, NAc, and PIR of stressed mice compared with control mice. This study provided direct evidence of 2-AG expression and changes, suggesting that 2-AG levels are increased in the ACC CP, NAc, and PIR when individuals are under chronic stress
Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial
Get PDF令和6年 浜松医科大学優秀論文賞：最優秀論文賞
受賞者：乾 直輝PURPOSE
We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy.
PATIENTS AND METHODS
Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety.
RESULTS
In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, ―1.3 to 13.9). The proportions of patients free of chemotherapyinduced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P< .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity.
CONCLUSION
The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.journal articl
A case of recurrent IgA vasculitis and nephritis treated effectively with tonsillectomy and methylprednisolone pulse therapy
Get PDFIgA血管炎（IgA vasculitis : IgAV）は自然軽快を期待できる良性疾患とされるが，紫斑病性腎炎（Henoch-Schönlein purpura nephritis : HSPN）合併の有無が患児の予後を左右する．血尿・蛋白尿が持続する場合には腎生検が行われ，組織学的重症度に応じて治療方針が決定される．多くのHSPN症例は免疫抑制治療により改善が見込まれるが，難治例の治療法は確立されていない．今回我々は，ステロイドパルス療法と多剤併用療法のみでは病勢を抑制できなかった反復性IgAVおよびHSPNの4歳女児に対し，扁桃摘出術・アデノイド切除術を施行後に再度ステロイドパルス療法と多剤併用療法を行った．その後はIgAVの再燃なく，尿所見も改善してゆき，約2年後に多剤併用療法を終了とした．難治性のIgAV/HSPNに対して，扁桃摘出術およびステロイドパルス療法は有効と考える．Although IgA vasculitis (IgAV) is considered to be a self-limited benign disease, its prognosis depends on the presence of a renal complication known as Henoch-Schönlein purpura nephritis (HSPN). When hematuria and/or proteinuria persists in HSPN patients, a kidney biopsy is performed and treatment content is determined by the pathological severity. Although most HSPN cases are expected to improve with immunosuppressive treatment, no treatment has been established for refractory HSPN cases. In this report, we present a 4-year-old girl with recurrent IgAV and HSPN that could not be controlled with methylprednisolone pulse therapy and multidrug combination therapy. She underwent tonsillectomy and adenoidectomy, followed by methylprednisolone pulse therapy and multidrug therapy. Thereafter, there was no recurrence of her IgAV, her urinary findings improved, and multidrug therapy was terminated 2 years later. We suggest that the combination of tonsillectomy and methylprednisolone pulse therapy may be effective for refractory IgAV/HSPN.journal articl
Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile.
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Importance of eosinophilic infiltration of the colonic mucosa in ulcerative colitis patients who are refractory to maintenance therapy: A prospective, single-center study
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Comparative analysis of gene expression profiles in the adipose tissue of obese adult mice with rapid infantile growth after undernourishment in utero
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
Alpha-synuclein interaction with UBL3 is upregulated by microsomal glutathione S-transferase 3, leading to increased extracellular transport of the alpha-synuclein under oxidative stress
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi