Search

Abstract The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most lethal forms of cancer. Although in the last decade, an increase in 5-year patient survival has been observed, the mortality rate remains high. As a first-line treatment for PDAC, gemcitabine alone or in combination (gemcitabine plus paclitaxel) has been used; however, drug resistance to this regimen is a growing issue. In our previous study, we reported MYC/glutamine dependency as a therapeutic target in gemcitabine-resistant PDAC secondary to deoxycytidine kinase (DCK) inactivation. Moreover, enrichment of oxidative phosphorylation (OXPHOS)-associated genes was a common property shared by PDAC cell lines, and patient clinical samples coupled with low DCK expression was also demonstrated, which implicates DCK in cancer metabolism. In this article, we reveal that the expression of most genes encoding mitochondrial complexes is remarkably upregulated in PDAC patients with low DCK expression. The DCK-knockout (DCK KO) CFPAC-1 PDAC cell line model reiterated this observation. Particularly, OXPHOS was functionally enhanced in DCK KO cells as shown by a higher oxygen consumption rate and mitochondrial ATP production. Electron microscopic observations revealed abnormal mitochondrial morphology in DCK KO cells. Furthermore, DCK inactivation exhibited reactive oxygen species (ROS) reduction accompanied with ROS-scavenging gene activation, such as SOD1 and SOD2. SOD2 inhibition in DCK KO cells clearly induced cell growth suppression. In combination with increased anti-apoptotic gene BCL2 expression in DCK KO cells, we finally reveal that venetoclax and a mitochondrial complex I inhibitor are therapeutically efficacious for DCK-inactivated CFPAC-1 cells in in vitro and xenograft models. Hence, our work provides insight into inhibition of mitochondrial metabolism as a novel therapeutic approach to overcome DCK inactivation-mediated gemcitabine resistance in PDAC patient treatment.

Hypertrophic pachymeningitis is a rare inflammatory condition that leads to the thickening of the dura mater, either due to unknown or identifiable secondary causes. Granulomatosis with polyangiitis is a notable causative agent, and hypertrophic pachymeningitis is the initial presentation in certain cases. The diagnosis of hypertrophic pachymeningitis is aided by contrast-enhanced MRI, although distinguishing between normal and abnormal dural enhancement can be challenging using contrast-enhanced T1WI. This study highlights the case of an 80-year-old woman diagnosed with hypertrophic pachymeningitis secondary to antineutrophil cytoplasmic antibody-associated granulomatosis with polyangiitis, where contrast-enhanced FLAIR played a crucial role in distinctly identifying abnormal dural enhancement and differentiating it from normal dura. In conclusion, although contrast-enhanced T1WI remains indispensable, contrast-enhanced FLAIR can serve as a valuable complementary tool in MRI study sequences for the diagnosis of hypertrophic pachymeningitis.

Abstract Tumor cells generally require large amounts of nucleotides, and thus activate de novo purine synthesis (dnPS). In the dnPS reactions, 10-formyltetrahydorofolate (10-fTHF) supplied by one-carbon metabolism is utilized as a formyl group donor. We focused on aldehyde dehydrogenase 1 family member L1 (ALDH1L1), which metabolizes 10-fTHF to tetrahydrofolate and whose expression is often attenuated in hepatocellular carcinoma (HCC). We generated ALDH1L1-expressing HuH-7 cells to perform metabolome analysis and found that intracellular levels of serine were reduced and glycine was increased. In addition, 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP), a dnPS intermediate, accumulated due to the consumption of 10-fTHF by ALDH1L1, which inhibited ZMP formylation. Importantly, ALDH1L1-expressing cells showed reduced ZMP sensitivity and higher mitochondrial activity. The suppression of mitochondrial serine catabolism by ALDH1L1 expression was speculated to be closely related to this phenotype. Gene set enrichment analysis utilizing The Cancer Genome Atlas data revealed that genes related to oxidative phosphorylation were enriched in HCC patients with high ALDH1L1 expression. Moreover, drug sensitivity data analysis demonstrated that HCC cell lines with low expression of ALDH1L1 were sensitive to ZMP and cordycepin, a structural analog of ZMP and AMP. Our study revealed that ZMP and AMP analogs might be effective in the pharmacotherapy of HCC patients with low expression of ALDH1L1.

Empyema is an infection of the pleural space that is classified into 3 stages. Video-assisted thoracoscopic surgery is recommended as the first-line approach for stage II acute empyema. The purpose of video-assisted thoracoscopic surgery is also achieved with hydrodissection and guidewire-dissection by breaking the septa mechanically in the pleural cavity. Hydrodissection and guidewire-dissection are techniques in which a contrast medium is administered at high pressure and a guidewire is inserted into the pleural cavity to break the septa, respectively. Hydrodissection and guidewire-dissection might be minimally invasive alternatives for the treatment of septated empyema.

Glial fibrillary acidic protein astrocytopathy is a form of autoimmune meningoencephalomyelitis. The presence of antibodies in spinal fluid against glial fibrillary acidic protein is necessary to diagnose the disease. There is no standard treatment and few cases of glial fibrillary acidic protein astrocytopathy have been reported. A 31-year-old healthy Japanese man presented to our emergency department with a 7-day history of fever and headache. He was in good general condition, without abnormalities on physical examination, and a general hematological examination revealed hyponatremia (130 mEq/L). Five days later, he was followed up and new subjective symptoms were noted: tremor in the right hand, constipation, sweating, and lightheadedness. Cerebrospinal fluid examination revealed a cell count of 57/μL (96 % mononuclear cells, 4 % multinuclear cells), elevated protein level (103 mg/dL), elevated adenosine deaminase level (15.0 U/L), negative polymerase chain reaction test results for herpes simplex virus and Mycobacterium tuberculosis, negative cerebrospinal fluid culture, and negative cerebrospinal fluid anti-acid bacteria culture, indicating aseptic meningitis. T1-weighted contrast-enhanced magnetic resonance imaging of the head showed a linear contrast effect perpendicular to the lateral ventricular wall and along the perivascular vessels spreading radially. Based on the presence of hyponatremia, history of movement disorder and autonomic symptoms, high adenosine deaminase level in cerebrospinal fluid, and findings on contrast-enhanced magnetic resonance imaging of the head, we suspected glial fibrillary acidic protein astrocytopathy and assessed anti-glial fibrillary acidic proteinαantibody in cerebrospinal fluid, which was positive, and diagnosed glial fibrillary acidic protein astrocytopathy. After careful follow-up with symptomatic treatment without immunosuppressive therapy, the fever, headache, tremor, and autonomic symptoms were improved over time. Contrast-enhanced magnetic resonance imaging of the head and findings of cerebrospinal fluid also showed improvement. glial fibrillary acidic protein astrocytopathy should be a differential diagnosis in patients with aseptic meningitis with movement disorders or autonomic symptoms and elevated cerebrospinal fluid adenosine deaminase. Careful follow-up without immunosuppressive treatment should be considered for patients with minimal neurologic symptoms as glial fibrillary acidic protein astrocytopathy may have a self-limiting course and resolve.

Background and Aims: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity. Methods: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed. Results: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort. Conclusion: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.

Abstract Background Foreign body ingestion is a common case in daily medical care, and it usually passes through the entire gastrointestinal tract naturally and is excreted in the feces. However, long and sharp foreign bodies may be difficult to pass naturally due to their shape. Here, we present a rare case of a duodenal foreign body, a toothbrush, that required laparoscopic surgical removal after a failed endoscopic attempt. Case presentation A 51-year-old male with intellectual disability presented to our hospital due to fever. Initially, he was diagnosed with aspiration pneumonia by chest X-ray and blood examination. However, abdominal X-ray examination suggested a foreign body, and a computed tomography scan revealed a toothbrush in the duodenum. Therefore, upper gastrointestinal endoscopy was immediately attempted to remove it, but it could not be safely removed because the handle part of the toothbrush seemed deeply embedded in the duodenal mucosa. Therefore, this case was diagnosed as duodenal incarceration of the toothbrush, and it was removed by laparoscopic surgery. The operation was performed safely, and the patient’s postoperative course was good without any complications. The extracted toothbrush was 15 cm in length. Conclusion We experienced a rare case of a duodenal foreign body, which was a toothbrush. The duodenal foreign body was safely removed by laparoscopic surgery for the first time.

Key Clinical Message A man hospitalized for cerebral infarction developed drug‐induced belly dancer syndrome, which improved after withdrawal of droxidopa and amantadine. Drugs that modulate dopamine neurotransmission have been reported to be associated with this syndrome. When belly dancer syndrome is suspected, clinicians should consider drug‐induced abdominal dyskinesia and medication withdrawal.

A woman in her 90's developed pain in the left buttock, along with a left buttock mass. Contrast-enhanced computed tomography revealed a mass in the left gluteus muscle, ureteral dilation, and pelvic ureteral disconnection. Retrograde urography revealed bending of the left ureter at the sciatic foramen. The patient was diagnosed with a ureterosciatic hernia and gluteal abscess and treated with ureteral stent placement and antibiotics. The patient experienced no recurrence during the follow-up period. The gluteal abscess was probably caused by urinary leakage due to ureteral obstruction, because the abscess and urine culture results were consistent.

Although immune checkpoint inhibitors (ICIs) can be used for lung cancer treatment, the activated immune response may cause immune-related adverse effects (irAEs). We present here a case of cytomegalovirus (CMV) enterocolitis during steroid therapy for an irAE. A 70-year-old man diagnosed with small-cell lung carcinoma (limited disease) received radiotherapy plus two chemotherapy cycles of cisplatin and etoposide. The tumor exhibited complete response but recurred after 3 years. After treatment with two cycles of carboplatin, etoposide, and atezolizumab, an inhibitors of programmed cell death receptor-1, he was switched to atezolizumab every 3 weeks for maintenance therapy. Diarrhea occurred after nine atezolizumab doses. With a strong suspicion of ICI-induced colitis, we administered methylprednisolone 500 mg for 3 days, followed by oral prednisolone 40 mg/day. Total colonoscopy during the treatment revealed mucosal inflammation of the total colon, suggesting immune-related colitis. Biopsies from the ulceration revealed crypt abscess with highly infiltrative plasma cells and lymphocytes. Furthermore, immunohistochemical staining showed positivity for CMV. With no improvement in watery diarrhea, the prednisolone dose was increased to 80 mg/day on the 11th day, and ganciclovir was additionally administered twice daily on the 26th day. On the 28th day, the patient had abdominal pain, and abdominal computed tomography revealed free air, resulting in the diagnosis of colon perforation. He underwent subtotal colectomy followed by ileostomy as emergency surgery. A colon specimen revealed colitis with CMV infection. We describe colon perforation in a patient with CMV enterocolitis complicated by refractory immune-related colitis.

Abstract Epigenetic alterations of chromatin structure affect chromatin accessibility and collaborate with genetic alterations in the development of cancer. Lysine demethylase 4B (KDM4B) has been identified as a JmjC domain‐containing epigenetic modifier that possesses histone demethylase activity. Although recent studies have demonstrated that KDM4B positively regulates the pathogenesis of multiple types of solid tumors, the tissue specificity and context dependency have not been fully elucidated. In this study, we investigated gene expression profiles established from clinical samples and found that KDM4B is elevated specifically in acute myeloid leukemia (AML) associated with chromosomal translocation 8;21 [t(8;21)], which results in a fusion of the AML1 and the eight‐twenty‐one (ETO) genes to generate a leukemia oncogene, AML1‐ETO fusion transcription factor. Short hairpin RNA‐mediated KDM4B silencing significantly reduced cell proliferation in t(8;21)‐positive AML cell lines. Meanwhile, KDM4B silencing suppressed the expression of AML1‐ETO‐inducible genes, and consistently perturbed chromatin accessibility of AML1‐ETO‐binding sites involving altered active enhancer marks and functional cis‐regulatory elements. Notably, transduction of murine KDM4B orthologue mutants followed by KDM4B silencing demonstrated a requirement of methylated‐histone binding modules for a proliferative surge. To address the role of KDM4B in leukemia development, we further generated and analyzed Kdm4b conditional knockout mice. As a result, Kdm4b deficiency attenuated clonogenic potential mediated by AML1‐ETO and delayed leukemia progression in vivo. Thus, our results highlight a tumor‐promoting role of KDM4B in AML associated with t(8;21).

PurposeUpregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.MethodsThe type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.ResultsA total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.ConclusionsHalf of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

Objectives: Many patients have endoscopic evidence of recurrent Crohn's disease (CD) 1 year after intestinal resection, and endoscopic lesions predict future clinical recurrence. The aim of this study was to describe some anastomotic lesions including changes in endoscopic features in CD patients and to discuss recurrence. We also compared anastomotic lesions in CD patients and in right-side colon cancer (rt-CC) patients. Methods: We enrolled patients with CD and rt-CC who underwent surgical resection between 2008 and 2014. Eleven CD patients underwent postoperative endoscopy at least twice, with the first time being from 6 months to 1 year after surgery and the second time being from 2 to 3 years after surgery. Eighty-six patients with rt-CC underwent postoperative endoscopy after approximately one year. Results: A total of 90.9% of CD patients had postoperative lesions around the anastomosis at the first postoperative ileocolonoscopy, which was markedly higher than that in rt-CC patients (3.5%, p

Abstract Background Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is often caused by Helicobacter pylori and has a good prognosis. Rarely, patients with MALT lymphoma may have gastric cancer and have a poor prognosis. Case presentation We herein report a case in which surgical treatment was achieved for a 72-year-old male patient with gastric and duodenal MALT lymphoma coexisting multiple gastric cancers. He underwent upper endoscopy for epigastric discomfort, which revealed mucosal erosion on the posterior wall of the middle body of the stomach, an elevated lesion on the duodenal bulb, and a raised tumor on the antrum of the stomach. He was diagnosed with gastric and duodenal MALT lymphoma with early gastric cancer. One month after H. pylori eradication, a second upper endoscopy revealed no improvement in the gastric or duodenal mucosa, and areas of strong redness with a shallow recess just below the cardia of the stomach. As a result, a diagnosis of gastric and duodenal MALT lymphoma with two gastric cancers was made. Total gastrectomy with proximal duodenum resection using intraoperative upper endoscopy and regional lymph node dissection was performed. Pathologically, gastric and duodenal MALT lymphoma and three gastric cancers were detected. Since one of them was an advanced cancer, he started taking S-1 after his general condition improved. Conclusion For early detection of gastric and duodenal MALT lymphoma or gastric cancer, appropriate upper endoscopy and a biopsy are important. It is necessary to select a suitable treatment, such as H. pylori eradication, endoscopic treatment, surgery, chemotherapy, and irradiation, according to the disease state.

The aim of this study was to determine whether important spatiotemporal variables in hurdle clearance change with different hurdle heights. Twelve male hurdlers (mean height, 1.75 ± 0.04 m) cleared hurdles set at different heights [10% higher (High) and 10% lower (Low) than the center of mass (CM)]; images were captured by six high-speed cameras, and each spatiotemporal variable was calculated. Thereafter, the difference in each spatiotemporal variable between High and Low and the relationship between the mean horizontal velocity from takeoff to landing [Hurdle clearance velocity (HC-v)] and each spatiotemporal variable were examined. Our findings indicated that values for flight time, flight time from hurdle to landing (2nd flight time), clearance time, release height on takeoff, peak height of the CM, and the difference in landing distance were greater in the High condition than in the Low condition. Moreover, a low rate of deceleration on takeoff and short 2nd flight time, clearance distance, and takeoff distance were more strongly related to HC-v in the condition High, whereas a low rate of deceleration on landing, short flight time from takeoff to hurdle (1st flight time), high release height on landing, and touchdown height on landing were more strongly related to HC-v in the Low condition. Therefore, coaches should consider these changes in spatiotemporal variables when changing hurdle heights based on age group or event. It should also be noted that, even when the hurdle heights are the same, the spatiotemporal variables that should be considered may differ depending on the height of the hurdler.

Abstract Background Pseudosarcomatous myofibroblastic proliferation is a rare proliferative lesion of the submucosal stroma characterized by myofibroblast proliferation and inflammatory cell infiltration, and is mainly reported in the urinary system. Case presentation We report a 65-year-old male who was referred to our emergency room with right-side iliac fossa pain. The pain gradually worsened for approximately 2 months, and rebound tenderness was positive. Blood examination showed severe inflammatory findings, and enhanced computed tomography revealed a heterogeneous contrast-enhancing mass lesion measured to be 55 × 50 mm in size at the lower right abdomen. Based on these results, the patient was diagnosed with appendicitis with an abdominal abscess. As the inflammation was severe, we drained the abscess before performing surgery. Approximately 1 month after the abscess diminished, interval appendectomy was performed. Macroscopic findings of the resected specimen showed a perforated diverticulum of the appendix and a small adjacent nodule measured to be 14 mm in size. Histopathological examination with hematoxylin and eosin staining revealed that the nodule consisted of fibroblast proliferation and inflammatory cell infiltration. Furthermore, immunohistochemical examination showed positive for smooth muscle actin and desmin and negative for S-100, c-kit, and anaplastic lymphoma kinase. Based on these histopathological results, we diagnosed the nodule as an unusual case of a pseudosarcomatous myofibroblastic proliferation associated with perforation of the diverticulum of the appendix. Conclusion Herein, we report a rare case of a pseudosarcomatous myofibroblastic proliferation that occurred in the appendix with diverticulitis.

Abstract Background Pneumoperitoneum commonly occurs as a result of a viscus perforation and usually presents with peritoneal signs requiring emergent laparotomy. Spontaneous pneumoperitoneum is a rare condition characterized by intraperitoneal gas with no clear etiology. Case presentation We herein report a case in which conservative treatment was achieved for an 83-year-old male patient with spontaneous pneumoperitoneum that probably occurred due to duodenal diverticulosis. He had stable vital signs and slight epigastric discomfort without any other signs of peritonitis. A chest radiograph and computed tomography showed that a large amount of free gas extended into the upper abdominal cavity. Esophagogastroduodenoscopy showed duodenal diverticulosis but no perforation of the upper gastrointestinal tract. He was diagnosed with spontaneous pneumoperitoneum, and conservative treatment was selected. His medical course was uneventful, and pneumoperitoneum disappeared after 6 months. Conclusion In the management of spontaneous pneumoperitoneum, recognition of this rare condition and an accurate diagnosis based on symptoms and clinical imaging might contribute to reducing the performance of unnecessary laparotomy. However, in uncertain cases with peritoneal signs, spontaneous pneumoperitoneum is difficult to differentiate from free air resulting from gastrointestinal perforation and emergency exploratory laparotomy should be considered for these patients.

Vertebral fracture with muscle hematoma is occasionally seen in practice. However, air-containing hematoma mimicking abscess has not been reported. We present an 87-year-old man with back pain after a fall. Computed tomography scan demonstrated vertebral fracture of L1 and low-density lesions with air bubble in the left crus of the diaphragm and left psoas muscle that were verified to be muscle hematoma. Muscle hematoma due to vertebral fracture can present radiological findings similar to an abscess. A characteristic “vertebral body cleft continuity sign” might be useful for differentiating between hematoma and abscess. Keywords: Vertebral fracture, Psoas abscess, Psoas hematoma, Abscess, Hematoma

Abstract Obesity increases the risk of metabolic disorders like diabetes mellitus and dyslipidemia. However, how metabolic status is sensed and regulates cellular behavior is unclear. Utx is an H3K27 demethylase that influences adipocyte function in vitro. To examine its role in vivo, we generated mice lacking Utx in adipocytes (UtxAKO). Although all UtxAKO mice grew normally on a normal chow diet (NCD), female UtxAKO mice on a high fat diet (HFD) showed striking reductions in body fat compared to control mice (Ctrl). Gene expression profiling of adipose tissues of HFD-fed UtxAKO female mice revealed decreased expression of rate-limiting enzymes of triacylglycerol synthesis but increased expression of those of cholesterol/steroid hormone synthesis. Moreover, these animals resisted adiposity induced by ovariectomy and exhibited increased estrogen in visceral adipose tissues. Thus, upon HFD feeding, Utx regulates lipid metabolism in adipose tissues by influencing the local hormonal microenvironment. Conversely, Utx deficiency skews lipid catabolism to enhance cholesterol/steroid hormone production and repress obesity.

Abstract Background Solitary adrenal metastasis from colorectal cancer is rare. Adrenal metastasis is usually detected with synchronous multiple metastases in other organs and is, therefore, considered to be unsuitable for surgical resection. The long-term outcomes of patients with solitary adrenal metastasectomy from colorectal cancer have been reported; however, the survival advantage has not been established. We herein report two cases of curative adrenal resection in patients with solitary adrenal metastasis from colorectal cancer who achieved long-term survival of > 9 years without recurrence after surgical resection. Case presentation The first case involved a 71-year-old man who underwent abdominoperineal rectal resection for rectal cancer. Preoperative CT revealed a mass in the right adrenal, which was growing after surgery. After chemotherapy the adrenal mass decreased in size, and adrenalectomy was performed at 8 months after the first surgery. A pathological examination confirmed metastasis from rectal cancer. The patient received adjuvant chemotherapy and is currently alive without recurrence at 9 years after the adrenalectomy. The second case involved a 53-year-old man who underwent sigmoidectomy for sigmoid colon cancer. Four years later, lobectomy was performed for isolated lung metastasis. Twenty months later, PET-CT revealed solitary metastasis in the left adrenal gland and adrenalectomy was performed. A histopathological examination revealed metastatic adenocarcinoma of sigmoid cancer. Postoperative chemotherapy was administered after adrenalectomy and the patient is currently alive and apparently disease-free at more than 9 years after undergoing adrenal metastasectomy. Conclusion Curative resection for solitary adrenal metastasis from colorectal cancer may be beneficial for survival.

Objectives: The aquarium sign is the name given to a large quantity of bubble-like echoes that suggests the presence of hepatic portal venous gas (HPVG). Few studies in the literature have addressed the relationship between the aquarium sign and HPVG. In some cases, HPVG can only be detected using ultrasonography. HPVG can be observed in a variety of conditions, including those that require emergency surgery, such as acute mesenteric ischaemia (AMI). Therefore, it is important to identify the presence of HPVG as soon as possible. Materials and methods: We report a case of the aquarium sign, where bubble-like echoes flowed from the right atrium towards the right ventricle, which was identified using bedside cardiac ultrasonography as part of a point-of-care ultrasound test. Results: This aquarium sign finding led to the diagnosis of AMI, which was confirmed using contrast-enhanced computed tomography (CT). Conclusion: The aquarium sign is a useful finding suggestive of HPVG and mesenteric ischaemia, which can be rapidly and easily observed using bedside cardiac ultrasonography. However, there are very few reports on the aquarium sign. The inability of other more cumbersome diagnostic imaging modalities, such as CT and magnetic resonance imaging, to detect HPVG emphasizes the utility and convenience of detecting the aquarium sign using bedside ultrasonography. This technique can lead to early detection of life-threatening diseases as well as improve the prognosis for patients. The diagnostic implications of the aquarium sign for HPVG are still unclear and require further research.

Abstract Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer‐related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co‐treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem‐like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

A 72-year-old woman presented with fever, rash and limb pain. Physical examination revealed systemic non-pitting edema, and painful edematous erythema on both forearms and thighs, and non-palpable petechia on her legs. These manifestations were suggestive of papular purpuric gloves and socks syndrome (PPGSS). Her serum anti-parvovirus B19 immunoglobulin M (IgM) was positive. To our knowledge, this is the oldest individual with typical parvovirus 19-associated PPGSS reported to date.

Blue laser/light imaging (BLI) is an image-enhanced endoscopy (IEE) technique that can provide an accurate diagnosis by closely observing the surface structure of various colonic lesions. However, complete correspondence between endoscopic images and pathological images has not been demonstrated. The aim of this study was to accurately compare endoscopic images and the pathological images using a three-dimensionally (3D) reconstructed pathological model. Continuous thin layer sections were prepared from colonic tissue specimens and immunohistochemically stained for CD34 and CAM5.2. Three-dimensional reconstructed images were created by superimposing immunohistochemically stained pathological images. The endoscopic image with magnifying BLI was compared with the top view of the 3D reconstructed image to identify any one-to-one correspondence between the endoscopic images and histopathological images using the gland orifices and microvessels as a guide. Using 3D reconstructed pathological images, we were able to identify the location on the endoscope image in cases of colonic adenocarcinoma, adenoma and normal mucosa. As a result, the horizontal plane of the endoscopic image and the vertical plane of the 2D pathological specimen were able to be compared, and we successfully determined the visible blood vessel depth and performed a detailed evaluation on magnifying BLI. Examples are as follows: (1) The median vasculature depth from the mucosal surface that could be recognized as vasculature on magnifying BLI was 29.4 μm. The median depth of unrecognizable vessels on magnifying BLI was 218.8 μm, which was significantly deeper than recognizable vessels. (2) Some brownish structures were suggested to potentially be not only dense vessels, vessel expansions, corrupted vessels but also bleeding or extravasation of erythrocytes. Overall, we demonstrated a new approach to matching endoscopic images and pathological findings using a 3D-reconstructed pathological model immunohistochemically stained for CD34 and CAM5.2. This approach may increase the overall understanding of endoscopic images and positively contribute to making more accurate endoscopic diagnoses.

Objectives: With endoscopic submucosal dissection and laparoscopic surgery, treatment for colorectal neoplasms has become minimally invasive. However, few studies have compared endoscopic submucosal dissection with laparoscopic surgery for colorectal neoplasms, excluding deeply invasive cancer on preoperative diagnosis. Methods: We retrospectively reviewed the files of patients who had undergone endoscopic submucosal dissection or laparoscopic surgery for colorectal neoplasms between November 2005 and December 2015. We limited patients who were not suspected preoperatively to have aggressive submucosal invasion >1,000 μm. Results: Ninety-five patients underwent endoscopic submucosal dissection and 37 underwent laparoscopic surgery. Cases of endoscopic submucosal dissection tended to involve rectal neoplasms more often than colonic neoplasms, shorter operative times, and shorter lengths of hospital stay compared with laparoscopic surgery. The perforation rate during colonic endoscopic submucosal dissection in the early period (November 2005 to December 2010) and late period (January 2011 to December 2015) was 14.8% and 2.9%, respectively. In all cases of perforation during colonic endoscopic submucosal dissection, the ability to maneuver the endoscope was compromised. Though tumors were larger in patients who underwent rectal endoscopic submucosal dissection compared with colonic endoscopic submucosal dissection, the perforation and postoperative bleeding rates with rectal endoscopic submucosal dissection were both 3.2%. The most common indication for laparoscopic surgery was difficulty performing endoscopic submucosal dissection. Serious complications were rare. Conclusions: For colonic neoplasms, laparoscopic surgery should be considered when endoscopic submucosal dissection is technically difficult in the early period. For rectal neoplasms, endoscopic submucosal dissection is desirable even for those of large size.

This study examined the relationship between the recognition of movement and actual movement during the standing long jump. A total of 11 healthy elementary school children from 10 to 11 years of age participated in this study. Participants conducted standing long jumps (the target movement) after receiving video instruction. They were then tested on their recognition of the target movement according to an image. A total of 12 markers were then attached to each participant to measure the actual movements taken during subsequent performances of the target movement. They were then tested on the recognition of their own movements (a self-evaluation). The results were as follows: maximum shoulder angle was observed prior to each jump; this became successively lower in the image review, actual movement, and self-evaluation procedures. Knee flexion angle successively decreased in the actual, target, self-evaluation, and image movements during the railway crossing procedure. While jumping, the maximum shoulder angle was significantly larger in the target movement than the actual ( P < .01) movement, but the actual movement was significantly lower than the image ( P < .001) and self-evaluation ( P < .001) movements. The angle between the perpendicular from the acromion and the line segment connecting the acromion to the lateral malleolus successively decreased in the target, image, self-evaluation, and actual movements. Thus, there were obvious points at which it was either easier or more difficult for subjects to recognize movements. Points of relative ease and difficulty were also identified during performance of the target movement.

The horizontally transferred chromosomal segments, which are the main source of genetic diversity among bacterial pathogens, are bound by the nucleoid protein H-NS, resulting in the formation of a nucleoprotein complex and the silencing of gene expression. The de-silencing or activation of virulence genes necessary for the colonization of enterohemorrhagic Escherichia coli is achieved mainly by the action of two regulators, Pch and Ler, which are encoded by horizontally transferred elements. Although Ler has been shown to activate transcription by counteracting H-NS silencing, the mechanism for Pch is poorly understood. We show here that Pch activates the LEE1 promoter and also enhances the Ler-mediated activation of other LEE promoters. Transcriptional activation was completely dependent on repression by the H-NS/StpA/Hha/YdgT complex, indicating that Pch-derived activation was achieved by alleviating H-NS-mediated silencing. Expression of pch reduced the binding of H-NS at LEE1 promoter and altered the nucleoprotein complex. Furthermore, in vitro reconstruction of the protein-DNA complex on LEE1 promoter DNA confirmed the exclusive effect of Pch on H-NS binding. These results demonstrated that Pch is another anti-silencing regulator and a modulator of H-NS-containing nucleoprotein complexes. Thus, the anti-silencing mechanism plays a key role in the coordinated regulation of virulence genes in EHEC.

The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers and is associated with cellular transformation, tumorigenesis, and metastatic progression. It is known that Mnks can phosphorylate eIF4E. Protein phosphatase 2A (PP2A) functions as a tumor suppressor, and it was previously suggested to regulate eIF4E phosphorylation. However, how PP2A regulates eIF4E phosphorylation has not been fully addressed. In this study, we have not only validated the role of PP2A in regulation of eIF4E phosphorylation but also demonstrated the mechanism underlying this process. Inhibition of PP2A using either okadaic acid or PP2A small interfering RNA (siRNA) increased eIF4E phosphorylation, which could be abolished by the presence of the Mnk inhibitor CGP57380 or deficiency of Mnk genes. Thus, Mnks are involved in PP2A-mediated regulation of eIF4E phosphorylation. Moreover, a dephosphorylation assay revealed that PP2A could directly dephosphorylate Mnk1 and eIF4E. m7GTP pull-down assay detected more eIF4G and phospho-eIF4E and less 4EBP-1 in PP2A siRNA-transfected cells than in control siRNA-transfected cells, indicating an increased cap binding of eIF4F complex. Accordingly, okadaic acid treatment or PP2A knockdown increased the levels of c-Myc and Mcl-1, which are proteins known to be regulated by a cap-dependent translation mechanism. Taken together, we conclude that PP2A negatively regulates eIF4E phosphorylation and eIF4F complex assembly through dephosphorylation of Mnk and eIF4E, thus suggesting a novel mechanism by which PP2A exerts its tumor-suppressive function.

Background. Murphy’s sign and Charcot’s triad are established clinical findings of acute cholecystitis and cholangitis, respectively, but both show low sensitivity and limited clinical application. We evaluated if indirect fist percussion of the liver improves the efficiency of diagnosing cholecystitis and cholangitis when used as a diagnostic adjunct. Methods. The presence/absence of right upper quadrant (RUQ) tenderness, Murphy’s sign, and pain induced by indirect fist percussion of the liver was assessed, and the results were compared with the definite diagnosis based on ultrasound and additional examinations in patients aged over 18 who visited our outpatient clinic with suspected hepatobiliary diseases. Results. Four hundred and eight patients were investigated, and 40 had hepatobiliary infection (acute cholecystitis: 10, acute cholangitis: 28, liver abscess: 1, and hepatic cyst infection: 1). The sensitivity of indirect fist percussion of the liver for diagnosing hepatobiliary infection was 60%, being significantly higher than that of RUQ tenderness (33%) and Murphy’s sign (30%), and its specificity was 85%. There was no significant improvement in sensitivity or diagnostic accuracy when Murphy’s sign was combined with indirect fist percussion of the liver. Conclusion. Indirect fist percussion-induced liver pain is a useful clinical finding to diagnose hepatobiliary infection, with high-level sensitivity.

A20 is a negative regulator of NF-κB, and mutational loss of A20 expression is involved in the pathogenesis of autoimmune diseases and B-cell lymphomas. To clarify the role of A20 in adult hematopoiesis, we generated conditional A20 knockout mice (A20(flox/flox) ) and crossed them with Mx-1Cre (MxCre (+)) and ERT2Cre (ERT2Cre (+)) transgenic mice in which Cre is inducibly activated by endogenous interferon and exogenous tamoxifen, respectively. A20(flox/flox) MxCre (+) (A20Mx) mice spontaneously exhibited myeloid proliferation, B cell apoptosis, and anemia with overproduction of pro-inflammatory cytokines. Bone marrow transplantation demonstrated that these changes were caused by hematopoietic cells. NF-κB was constitutively activated in A20Mx hematopoietic stem cells (HSCs), which caused enhanced cell cycle entry and impaired repopulating ability. Tamoxifen stimulation of A20(flox/flox) ERT2Cre (+) (A20ERT2) mice induced fulminant apoptosis and subsequent myeloproliferation, lymphocytopenia, and progressive anemia with excessive production of pro-inflammatory cytokines, as observed in A20Mx mice. These results demonstrate that A20 plays essential roles in the homeostasis of adult hematopoiesis by preventing apoptosis and inflammation. Our findings provide insights into the mechanism underlying A20 dysfunction and human diseases in which A20 expression is impaired.

Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex. Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers. Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.

Multiwavelength, high resolution micro-Raman spectroscopy was applied to in-line process monitoring and diagnostics of undoped and B-doped Si1-xGex epitaxy on Si(100) device wafers. This noncontact technique was used to monitor the Ge content, B concentration and thickness of single and double Si1-xGex epitaxial layers. Epitaxial process problems were diagnosed nondestructively. Raman peak positions and full-width-at-half-maximum of the Si-Si peak(s) from the Si1-xGex epitaxial layer(s) and Si substrates, in the wavenumber range of 475 ∼ 535 cm-1, were monitored under ultraviolet and visible excitation wavelengths. The Ge content, B concentration and Si1-xGex epitaxial film structures were verified by secondary ion mass spectroscopy (SIMS) depth profiling results. In-line monitoring of Si-Si and Si Raman peaks is very effective in noncontact material property characterization, epitaxial process optimization, and quality control applications.

Non-contact monitoring of Ge content and B concentration in single and double Si1-xGex epitaxial layers on Si(100) device wafers was attempted using high-resolution, multiwavelength micro-Raman spectroscopy. The Ge content and B concentration determined by secondary ion mass spectroscopy (SIMS) depth profiling showed very strong correlation with the position and full-width-at-half-maximum of the Si-Si peak from the Si1-xGex epitaxial layers as determined by Raman measurements. High resolution X-ray diffraction (HRXRD) characterization was done for all wafers to determine Ge and B sensitivity and form comparisons with Raman and SIMS analysis. The non-destructive, in-line monitoring of Ge content and B concentration of single and double Si1-xGex epitaxial layers with thickness ranging from 5 ∼ 120 nm, on small area monitoring pads, was successfully demonstrated by multiwavelength micro-Raman spectroscopy during epitaxial process optimization, material property verification, and quality control applications.

Fork-head box protein A1 (FOXA1) is a "pioneer factor" that is known to bind to the androgen receptor (AR) and regulate the transcription of AR-specific genes. However, the precise role of FOXA1 in prostate cancer (PC) remains unknown. In this study, we report that FOXA1 plays a critical role in PC cell proliferation. The expression of FOXA1 was higher in PC than in normal prostate tissues (P = 0.0002), and, using immunohistochemical analysis, we found that FOXA1 was localized in the nucleus. FOXA1 expression levels were significantly correlated with both PSA and Gleason scores (P = 0.016 and P = 0.031, respectively). Moreover, FOXA1 up-regulation was a significant factor in PSA failure (P = 0.011). Depletion of FOXA1 in a prostate cancer cell line (LNCaP) using small interfering RNA (siRNA) significantly inhibited AR activity, led to cell-growth suppression, and induced G0/G1 arrest. The anti-proliferative effect of FOXA1 siRNA was mediated through insulin-like growth factor binding protein 3 (IGFBP-3). An increase in IGFBP-3, mediated by depletion of FOXA1, inhibited phosphorylation of MAPK and Akt, and increased expression of the cell cycle regulators p21 and p27. We also found that the anti-proliferative effect of FOXA1 depletion was significantly reversed by simultaneous siRNA depletion of IGFBP-3. These findings provide direct physiological and molecular evidence for a role of FOXA1 in controlling cell proliferation through the regulation of IGFBP-3 expression in PC.

Objective. The aim of this study is to develop a prognostic model capable of predicting the probability of significant upgrading among Japanese patients. Methods. The study cohort comprised 508 men treated with RP, with available prostate-specific antigen levels, biopsy, and RP Gleason sum values. Clinical and pathological data from 258 patients were obtained from another Japanese institution for validation. Results. Significant Gleason sum upgrading was recorded in 92 patients (18.1%) at RP. The accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 88.9%. Overall AUC was 0.872 when applied to the validation data set. Nomogram predictions of significant upgrading were within 7.5% of an ideal nomogram. Conclusions. Nearly one-fifth of Japanese patients with prostate cancer will be significantly upgraded. Our nomogram seems to provide considerably accurate predictions regardless of minor variations in pathological assessment when applied to Japanese patient populations.

The p400 E1A-associated protein, which mediates H2A.Z incorporation at specific promoters, plays a major role in cell fate decisions: it promotes cell cycle progression and inhibits induction of apoptosis or senescence. Here, we show that p400 expression is required for the correct control of ROS metabolism. Depletion of p400 indeed increases intracellular ROS levels and causes the appearance of DNA damage, indicating that p400 maintains oxidative stress below a threshold at which DNA damages occur. Suppression of the DNA damage response using a siRNA against ATM inhibits the effects of p400 on cell cycle progression, apoptosis, or senescence, demonstrating the importance of ATM-dependent DDR pathways in cell fates control by p400. Finally, we show that these effects of p400 are dependent on direct transcriptional regulation of specific promoters and may also involve a positive feedback loop between oxidative stress and DNA breaks since we found that persistent DNA breaks are sufficient to increase ROS levels. Altogether, our results uncover an unexpected link between p400 and ROS metabolism and allow deciphering the molecular mechanisms largely responsible for cell proliferation control by p400.

This study aimed to clarify the kinetics of the relative vertical momentum to the proximal joint of each free limb and their contribution to the increase in the centre of mass height at the take-off of hurdle clearance, as well as their relationship with take-off variables. Thirteen male hurdlers cleared one hurdle at the height of their centre of mass, and their attempts were filmed using six high-speed cameras. The hurdle height was 96.54 ± 2.63 cm (55.35 ± 0.29% of body height). The approach distance was set at 15 m and adjusted by each hurdler in the range of 10-50 cm so as not to involve any noticeable step length adjustment before the take-off. The combined free limb relative vertical momentum tended to increase until mid-support and was maintained until the toe off. The smaller the whole-body vertical momentum at the toe off and the increase in relative vertical momentum of the lead leg during the take-off, the higher the take-off velocity, the shorter the support time, and the smaller the deceleration. The higher the relative vertical momentum of the forward swing arm during touchdown and the smaller the relative vertical momentum increase of the combined free limb and the forward swing arm during the take-off, the smaller the deceleration. In conclusion, hurdlers should reduce the increase in whole-body vertical momentum at the take-off by suppressing the increase in relative vertical momentum of the lead leg and the forward swing arm. [ABSTRACT FROM AUTHOR]