Search

Background A simple measure of immune cytolytic activity (CYT) base on mRNA expression levels of two genes, GZMA and PRF1, was recently reported. Here, we aimed to evaluate the CYT score's potential as a measure of antitumor immunity and predictor of clinical outcome in gastric cancer (GC) patients. Materials and Methods We evaluated the correlations between tumor‐infiltrating immune cells and the CYT score in 238 GC samples from The Cancer Genome Atlas (TCGA). Next, we investigated CYT score associations with molecular subtypes, somatic mutation load, and immune checkpoint molecules in GC samples from TCGA and Asian Cancer Research Group (ACRG). Moreover, we evaluated the clinical significance of the CYT score calculated by reverse transcription (RT)‐quantitative PCR (qPCR) data in 123 GC samples and the association of the CYT score with the response to anti‐PD‐1 therapy in 7 GC samples from Kyushu University Hospital. Results The CYT score positively correlated with the proportions of tumor‐infiltrating CD8+ T cells and macrophages and negatively correlated with the proportion of regulatory T cells in GC tissues. A high CYT score was associated with common immune checkpoint molecules, a high mutation, the Epstein–Barr virus subtype, and the microsatellite instability subtype in GC. Moreover, a low CYT score was a poor prognosis factor in patients with GC. Finally, the CYT score was higher in a responder to anti‐PD‐1 therapy compared to nonresponders. Conclusion The CYT score reflects antitumor immunity and predicts clinical outcome in GC patients., High CYT score was associated with tumor‐infiltrating CD8+ T cells, EBV, MSI‐H, high tumor mutation load, and upregulated immune checkpoint molecules in gastric cancer. Moreover, the CYT score was associated with prognosis and response to the anti‐PD‐1 antibody in gastric cancer patients.

ARMM is a disease with a poor prognosis. ARMM is often diagnosed at an advanced stage, and the 5-year survival rate of ARMM is

A 75-year-old male was admitted to our hospital because of bile duct stenosis. He had no medical history of autoimmune disease. The level of tumor markers, serum IgG, and IgG4 were within normal ranges. Computed tomography showed perihilar and distal bile duct stenosis and wall thickening without swelling or abnormal enhancement of the pancreas. Endoscopic retrograde cholangiopancreatography showed perihilar and distal bile duct stenosis. A biopsy and cytology from the distal bile duct stenosis suggested adenocarcinoma, and cytology from the perihilar bile duct also suggested adenocarcinoma. A preoperative diagnosis of perihilar and distal bile duct cancer was made, and the patient underwent left hepatectomy and pancreaticoduodenectomy. Resected specimens showed wall thickening in the perihilar and distal bile duct; however, tumors were unclear. A histopathological examination revealed lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis in the perihilar and distal bile ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the perihilar and distal bile ducts. Lymphoplasmacytic infiltration, inflammatory change, storiform fibrosis, and obliterative phlebitis were shown in the pancreas. A final diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC) with autoimmune pancreatitis was made. We herein report a case in which a preoperative diagnosis of IgG4-SC was difficult due to normal serum IgG4 levels and no obvious pancreatic lesion.

Metatropic dysplasia is a congenital skeletal dysplasia characterized by severe platyspondyly, dumbbell-like deformity of long tubular bones, and progressive kyphoscoliosis with growth. It is caused by mutations in the gene TRPV4, encoding the transient receptor potential vanilloid 4, which acts as a calcium channel. Many heterozygous single base mutations of this gene have been associated with the disorder, showing autosomal dominant inheritance. Although abnormal endochondral ossification has been observed by histological examination of bone in a patient with lethal metatropic dysplasia, the etiology of the disorder remains largely unresolved. As dental pulp stem cells (DPSCs) are mesenchymal stem cells that differentiate into bone lineage cells, DPSCs derived from patients with congenital skeletal dysplasia might be useful as a disease-specific cellular model for etiological investigation. The purpose of this study was to clarify the pathological association between TRPV4 mutation and chondrocyte differentiation by analyzing DPSCs from a patient with non-lethal metatropic dysplasia. We identified a novel heterozygous single base mutation, c.1855C>T in TRPV4. This was predicted to be a missense mutation, p.L619F, in putative transmembrane segment 5. The mutation was repaired by CRISPR/Cas9 system to obtain isogenic control DPSCs for further analysis. The expression of stem cell markers and fibroblast-like morphology were comparable between patient-derived mutant and control DPSCs, although expression of TRPV4 was lower in mutant DPSCs than control DPSCs. Despite the lower TRPV4 expression in mutant DPSCs, the intracellular Ca2+ level was comparable at the basal level between mutant and control DPSCs, while its level was markedly higher following stimulation with 4α-phorbol 12,13-didecanoate (4αPDD), a specific agonist for TRPV4, in mutant DPSCs than in control DPSCs. In the presence of 4αPDD, we observed accelerated early chondrocyte differentiation and upregulated mRNA expression of SRY-box 9 (SOX9) in mutant DPSCs. Our findings suggested that the novel missense mutation c.1855C>T of TRPV4 was a gain-of-function mutation leading to enhanced intracellular Ca2+ level, which was associated with accelerated chondrocyte differentiation and SOX9 upregulation. Our results also suggest that patient-derived DPSCs can be a useful disease-specific cellular model for elucidating the pathological mechanism of metatropic dysplasia. Keywords: Chondrocyte differentiation, Dental pulp stem cell, Metatropic dysplasia, Transient receptor potential vanilloid 4

Benzo-15-crown-5 and dipicolylamine are contained as the binding sites in a ditopic azoprobe (15C5-Azo-n-dpa). However, the selectivities of guest-induced supramolecular chirality for cations and anions were dramatically altered by a slight change in the spacer length of (15C5-Azo-n-dpa)2–γ-CyD complexes in water.

Metatropic dysplasia is a congenital skeletal dysplasia characterized by severe platyspondyly, dumbbell-like deformity of long tubular bones, and progressive kyphoscoliosis with growth. It is caused by mutations in the gene TRPV4, encoding the transient receptor potential vanilloid 4, which acts as a calcium channel. Many heterozygous single base mutations of this gene have been associated with the disorder, showing autosomal dominant inheritance. Although abnormal endochondral ossification has been observed by histological examination of bone in a patient with lethal metatropic dysplasia, the etiology of the disorder remains largely unresolved. As dental pulp stem cells (DPSCs) are mesenchymal stem cells that differentiate into bone lineage cells, DPSCs derived from patients with congenital skeletal dysplasia might be useful as a disease-specific cellular model for etiological investigation. The purpose of this study was to clarify the pathological association between TRPV4 mutation and chondrocyte differentiation by analyzing DPSCs from a patient with non-lethal metatropic dysplasia. We identified a novel heterozygous single base mutation, c.1855C>T in TRPV4. This was predicted to be a missense mutation, p.L619F, in putative transmembrane segment 5. The mutation was repaired by CRISPR/Cas9 system to obtain isogenic control DPSCs for further analysis. The expression of stem cell markers and fibroblast-like morphology were comparable between patient-derived mutant and control DPSCs, although expression of TRPV4 was lower in mutant DPSCs than control DPSCs. Despite the lower TRPV4 expression in mutant DPSCs, the intracellular Ca2+ level was comparable at the basal level between mutant and control DPSCs, while its level was markedly higher following stimulation with 4α-phorbol 12,13-didecanoate (4αPDD), a specific agonist for TRPV4, in mutant DPSCs than in control DPSCs. In the presence of 4αPDD, we observed accelerated early chondrocyte differentiation and upregulated mRNA expression of SRY-box 9 (SOX9) in mutant DPSCs. Our findings suggested that the novel missense mutation c.1855C>T of TRPV4 was a gain-of-function mutation leading to enhanced intracellular Ca2+ level, which was associated with accelerated chondrocyte differentiation and SOX9 upregulation. Our results also suggest that patient-derived DPSCs can be a useful disease-specific cellular model for elucidating the pathological mechanism of metatropic dysplasia., Highlights • Dental pulp stem cells from a patient with metatropic dysplasia were analyzed. • A novel heterozygous single base mutation, c.1855C > T, was identified in TRPV4. • The mutation was repaired by gene editing to obtain isogenic control cells. • The intracellular Ca2+ level was enhanced in mutant cells by 4αPDD. • Chondrocyte differentiation was enhanced in mutant cells by 4αPDD.

Objective Hyperbilirubinemia in patients with biliary atresia causes deciduous tooth injuries such as green pigmentation and dentin hypoplasia. In patients with biliary atresia who received liver transplantation, tooth structure appears to be recovered radiographically. Nevertheless, little is known about cellular mechanisms underlying bilirubin-induced damage and suppression of deciduous tooth formation. In this study, we examined the effects of bilirubin in stem cells from human exfoliated deciduous teeth (SHED) in vitro. Materials and methods SHED were cultured under exposure to excess of bilirubin and then interruption of bilirubin stimulation. Results Bilirubin induced cell death and inhibited the odontogenic capacity of SHED by suppressing AKT and extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathways and enhancing nuclear factor kappa B p65 (NF-κB p65) pathway. The interruption of bilirubin stimulation reduced cell death and recovered the inhibited odontogenic capacity of bilirubin-damaged SHED. The bilirubin interruption also normalized the impaired AKT, ERK1/2, and NF-κB p65 signaling pathways. Conclusion These findings suggest that tooth hypodontia in patients with hyperbilirubinemia might be due to bilirubin-induced cell death and dentinogenic dysfunction of odontogenic stem cells via AKT, ERK1/2, and NF-κB pathways and also suggested that bilirubin-induced impairments in odontogenic stem cells were reversible when bilirubin stimulation is interrupted.

This paper reports the microstructural analysis of 20-μm-thick Al0.5Ga0.5N with improved crystalline quality owing to the use of a Mg-doped AlN underlying layer. The threading dislocation density in 20-μm-thick Al0.5Ga0.5N on Mg-doped AlN was 8.6×108cm-2, which is about one-fifth lower than that of Al0.5Ga0.5N on an undoped AlN underlying layer. The microstructural analysis was carried out to clarify dislocation behaviours in the Al0.5Ga0.5N layer on the Mg-doped AlN underlying layer. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Microstructural analysis was carried out to clarify the compositional dependence of the generation of dislocations in AlxGa1-xN on an underlying AlN layer grown by metalorganic vapor phase epitaxy. When the film thickness is less than 1.5 μm, the threading dislocation density (TDD) increases with decreasing AlN molar fraction. However, when the film thickness exceeds 1.5 μm, TDD becomes maximum at x around 0.5. The growth of AlGaN on a grooved AlN template is effective in reducing TDD for all AlN molar fractions. TDD in AlGaN, which is close to binaries such as GaN and AlN, is a few 107 cm–2, while for the intermediate composition with x around 0.5, TDD is still at mid 108 cm–2. The activation energy of Mg in AlGaN is found to show a strong Mg concentration dependence with a negative one-third power law in Al0.25Ga0.75N and Al0.5Ga0.5N as well as in GaN. Overdoping of Mg causes an increase in the activation energy for every composition; from this, the optimum Mg concentration for realizing the highest hole concentration can be deduced. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

肺腫瘤に対する治療方針の決定に際してはその質的診断が重要になる. 特に悪性腫瘍の術前検査時や切除後に孤立性の肺腫瘤が発見された場合は原発性肺癌, 転移性肺腫瘍, 良性肺腫瘤の鑑別が必須であり, 鑑別診断のためには第一に発生頻度を把握しておく必要がある. 2000年1月から2003年6月までに当院で悪性腫瘍の術前検査あるいは術後の経過観察中に発見され切除された孤立性肺腫瘤症例56例 (男性38例, 女性18例, 平均65.3歳) を検討した. 初回悪性腫瘍の手術から肺切除までの平均観察期間は33.5カ月で, 初回悪性腫瘍は大腸癌19例 (33.9%), 胃癌18例 (32.1%), 乳癌7例 (12.5%), その他12例であり, 結果は原発性肺癌30例 (53.6%), 転移性肺腫瘍15例 (26.8%), 良性肺腫瘤11例 (19.6%) であった. 悪性腫瘍の術後といえども原発性肺癌の発生に留意する必要があると考えられた.

胃癌術後の中心静脈カテーテル菌血症に起因したと考えられた化膿性脊椎炎の2例を経験した.症例1は79歳の男性で幽門側胃切除術と肝部分切除術を施行,縫合不全のため中心静脈カテーテルを挿入した.挿入後53日目に39.1°Cの発熱を認め,カテーテルを抜去し解熱を確認した.抜去後2日目から腰背部痛が出現, 3カ月後に腰背部痛の増悪と歩行困難を認め化膿性脊椎炎と診断された.症例2は86歳の男性で幽門側胃切除術を施行,術後経口摂取不良のために中心静脈カテーテルを挿入した.挿入後23日目に38.9°Cの発熱を認め,カテーテルを抜去し解熱を確認した.抜去後7日目に腰痛が出現し化膿性脊椎炎と診断された. 2例とも動脈血培養で菌血症の起炎菌を確認した.化膿性脊椎炎の起炎菌である可能性が高いと判断し保存的治療にて軽快退院した.カテーテル菌血症後に腰痛を認めた場合,化膿性脊椎炎を念頭に置く必要があると考えられた.

We report a novel supramolecular chirality induced by the twisted structural change of two ditopic azoprobes (15C5-Azo-dpa) inside the chiral cavity of γ-cyclodextrin (γ-CyD) due to multi-point recognition of guest ions by 15C5-Azo-dpa molecules in water.

症例は63歳,男性.胃体中部の3型胃癌に対して胃亜全摘術, Billroth I法による再建術を施行し,残胃内に経鼻胃管を留置した.術後2日目より発熱を認め,血液検査でも炎症所見の上昇を認めた.腹部CT検査を行ったが術後変化による少量の腹水貯留を認めるのみであった.術後5日目,腹腔内に留置したドレーンより混濁した黄色の排液を認めたため経鼻胃管を用いた残胃造影検査を施行した.胃管先端が鋳型状に残胃大彎側から突出し,造影剤の胃外漏出を認めたため,胃管による残胃穿孔と診断した.腹腔内ドレーンによる漏出液のドレナージは良好であったため保存的加療が可能であると判断し,高カロリー輸液および抗生剤投与を行った.遺残膿瘍など他の合併症を併発することなく,術後34日目に経口摂取を開始し,術後44日目に軽快退院した.

真性腸石の本邦報告例は41例に過ぎない.多発性小腸狭窄に合併した真性腸石の1例を報告した.症例は55歳男性,主訴は腹痛.約10年前より腹痛及び腸管蠕動不全を繰り返したが,その都度保存的に軽快した.近医にて胆石症を指摘され当科紹介となった.腹部CTにて,小腸結石を2個認めた.手術当日再度CTを施行し,回腸末端部に1個の結石を確認した.胆石症および小腸結石の術前診断にて腹腔鏡補助下手術を行った.腹腔内に多発する小腸狭窄を認め,回盲部より約160cmの回腸狭窄部に腸石の嵌頓を認めた.消化管に瘻孔は認めなかった.腸石摘出後,胆嚢摘出術を施行した.腸石は最大径4cm,重量10gで,結石分析の結果から胆汁酸を主成分とする真性腸石と判断した.真性腸石過去報告例では,腸内容うっ滞を伴う憩室・狭窄・盲嚢の併存例が多く,自験例も多発する小腸狭窄が原因と考えられた.

We fabricated and evaluated GaN/AlGaN multi-quantum wells (MQWs) and ultraviolet laser diodes (UV LDs) on high and low dislocation density underlying layers by epitaxial lateral overgrowth (ELO) method. We analyzed the internal quantum efficiency (IQE) versus carrier concentration characteristics quantitatively by excitation intensity dependent photoluminescence method. The IQE of the MQWs on the ELO AlGaN is 75% when the carrier density is 1x1019 cm-3. We demonstrated the UV LD on the ELO AlGaN. However, the UV LD on flat AlGaN did not operate. Also, we investigated the internal loss (αi) and the IQE multiplied the injection efficiency by changing the reflectivity of the facets. The results showed that the internal loss is 6 cm-1, and the IQE multiplied by the injection efficiency is 18% (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Internal quantum efficiency (IQE) of GaN/AlGaN multi quantum wells on the low dislocation density Al0.25Ga0.75N grown by epitaxial lateral overgrowth (ELO) and facet controlled epitaxial lateral overgrowth were investigated by excitation intensity dependent photoluminescence measurement. The threading dislocation density decreased from 4x109cm-2 to 2x108cm-2 by using ELO method, then the IQE was much improved from 5% to 40% when the carrier density was 1x1018cm-3. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We report on a new technology for growing low-dislocation-density AlGaN in which a Mg-doped AlN underlying layer is used. By growing AlxGa1-xN on AlN:Mg with AlN molar fractions x of 0.3, 0.5 and 0.7, the density of misfit dislocations is much reduced compared with that in the case of growing AlGaN on undoped AlN. In addition, the surface becomes atomically flat. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Microstructural analysis was conducted to observe Mg-related defects in highly Mg-doped AlN on an undoped AlN layer grown by metalorganic vapor phase epitaxy. Pyramidal defects at a density of 10 15 cm -3 were observed in the Mg-doped AlN layer with a Mg concentration of 2.5 × 10 19 cm -3 . The size and density of the pyramidal defects decreased at a low Mg-doped AlN layer with a Mg concentration. When the Mg concentration is high, defects of different shapes were formed in the Mg-doped AlN layer.

Internal and external quantum efficiency and injection efficiency of nitride-based UV/DUV devices were investigated. Non radiative component in the photoluminescence and electroluminescence is found to be strongly correlated with the dislocation density.

A 45-year-old woman, complaining of back pain and bloody stool was given a diagnosis of poorly differentiated adenocarcinoma of the rectum with disseminated carcinomatosis to bone marrow and disseminated intravascular coagulation syndrome (DIC). We started chemotherapy using mFOLFOX-6 with simultaneous DIC treatment. After we confirmed that DIC had improved following 2 courses of mFOLFOX-6, bevacizumab was added to mFOLFOX-6. Laboratory studies revealed a serum CEA level of 314.4ng/ml, which improved to 4.6ng/ml after a total of 6 courses of chemotherapy. Colonoscopy findings showed almost normal rectal mucosa after a total of 10 courses of chemotherapy. Outpatient treatment was started after 5 courses of chemotherapy, and was continuing according to schedule at 7 months from the onset of this disease.

The prognosis of metastatic or recurrent GISTs is poor, because these tumors resist chemotherapy and radiotherapy. We report a patient with recurrent GIST who underwent molecularly targeted therapy with imatinib, a novel oral tyrosine kinase inhibitor. A 64-year-old man presented with large intra-abdominal mass. The patient had a history of jejunostomy with colostomy for intestinal GIST. The abdominal mass was phi3 x 3.5 cm in size with ascites at Douglas, as determined by computed tomography, and was diagnosed as a peritoneal relapse of GIST. Treatment with imatinib daily was started. After 1 month of treatment with imatinib, reduction of the abdominal tumor began to be recognized on palpation. Computed tomographic scanning at 11 months revealed that the tumor had completely disappeared. The major side effect was drug eruption,which was easily manageable with 2 weeks drug holidays. Imatinib shows promise as a safe and effective drug for the treatment of patients with recurrent GISTs.

Objectives: For the histological diagnosis of small lung cancers of 10 mm or less in diameter (≤10), resection by video-assisted thoracic surgery (VATS) with computed tomography (CT)-guided marking is feasible. One problem is that a small number of these pulmonary nodules are malignant. We retrospectively analyzed CT images of pulmonary nodules to find better criteria to select candidates for resection among patients with small pulmonary nodules. Methods: Ninety-four patients with indeterminate peripheral pulmonary nodules underwent wedge resection by VATS. High-resolution CT using a 1.25 mm slice included the area of lesions. Nodules were classified by size (≤10, 11 to 22,>20 mm) and whether they had a ground-glass opacity (GGO) component. Results: The histology of all 94 nodules showed 52 primary lung cancers, 6 metastatic tumors, 5 benign tumors, 8 intrapulmonary lymph nodes, and 23 inflammatory nodules. Ninety-three percent of nodules larger than 20 mm, 75% of nodules 10 to 20 mm, and 43% of nodules ≤10 mm were malignant. Introducing a classification according to GGO component to nodules, malignancy was detected in 88% of nodules with a GGO component and in 30% of nodules without a GGO component among nodules ≤10 mm. Nodules ≤10 mm with a GGO component showed a statistically significant (p

A 79-year-old man was admitted for advanced transverse colon cancer with large bowel obstruction. Twelve years earlier he underwent a total gastrectomy with Roux-en Y reconstruction for gastric cancer. No metastasis was detected preoperatively. Exploratory laparotomy revealed massive direct invasion of the mesenterium of the jejunum for Roux-en Y reconstruction. The primary lesion was unresected and transverse colostomy was made. Systemic chemotherapy with 5-fluorouracil and l-leucovorin was scheduled for a total of 4 courses postoperatively. After completion of this chemotherapeutic regimen, a CT scan and colonofiberscopy revealed the primary lesions had disappeared, and a histological examination of biopsy confirmed that the patient had achieved a complete remission (CR). There was no severe side effect during chemotherapy. The patient is presently enjoying a good general condition and has been free from any sign of recurrence.

We found different behaviors of misfit dislocations in a Ga0.83In0.17N single layer and in Ga0.83In0.17N/Ga0.93In0.07N superlattices, both on GaN substrates. In the case of the single layer, misfit dislocations were formed at the GaInN/GaN interfaces and extended through the GaInN layer to the surface. In contrast, the misfit dislocations in the superlattices are bent laterally at interfaces between the Ga0.83In0.17N and Ga0.93In0.07N layers. In addition, most of the dislocations do not reach the surface owing to the formation of dislocation loops. As a result, the dislocation density at the surface of the GaInN superlattice sample was 5×107 cm-2.

Two strain relaxation processes have been observed in AGaN layers grown on thick AlN templates. In Process I, a-type threading dislocations (TDs) with b= 1/3 from the AlN underlayer are inclined away from the [0001] axis toward the directions when they enter the AlGaN film, forming dislocation line projection perpendicular to the Burger vector. In Process II, a+c-type TDs from the AlN underlayer with Burgers vector of b= 1/3 glide on {0111} planes when they enter the AlGaN film to generate interfacial misfit dislocations lying along the directions at the AlGaN/AlN interface.