A Case of Lobulated and Pedunculated Duodenal Hyperplastic Polyp Treated with Snare Polypectomy

We report herein the case of a lobulated and pedunculated hyperplastic polyp in the third portion of the duodenum causing anemia and occult blood in stools, which was detected by capsule endoscopy (CE) and treated with snare polypectomy. A 71-year-old man was referred to our hospital because of anemia and occult blood in stools. Three months earlier, he had been admitted to another hospital because of hemorrhage from gastric antral vascular ectasia (GAVE). Despite being treated for GAVE, hemoglobin decreased gradually. Esophagogastroduodenoscopy (EGD) and colonoscopy revealed no source of bleeding. However, CE revealed a polyp at the distal duodenum. Barium meal and EGD revealed a lobulated and pedunculated polyp in the third portion of the duodenum. The polyp was treated with snare polypectomy. Histopathological examination of the polyp revealed hyperplasia. After treatment of the polyp, the anemia improved gradually. To our knowledge, there are only 6 reported cases of a duodenal hyperplastic polyp, including our case. The polyp was pedunculated in only 2 cases and lobulated only in our case. Moreover, our case was diagnosed by CE. When a patient presents with anemia or obscure gastrointestinal bleeding undiagnosed by EGD and colonoscopy, CE is useful for detecting the bleeding lesion

Spondylolysis with pedicle fracture

We describe successful surgical treatment in a case of L5 unilateral spondylolysis with contralateral pedicle stress fracture that was not resolved by conservative treatment in a high-performing college baseball player. The 20-year-old man presented with left low back pain that stopped his sports activities. Over the previous year, he had experienced a couple of episodes of pain that subsided with cessation of sports but reappeared after a return to sports. Computed tomography and magnetic resonance imaging revealed a right terminal stage pars fracture and a left pedicle stress fracture at L5. The pain originated from the left pedicle fracture, with no pain from the right unilateral spondylolysis. Given that conservative treatment for 1 year had not been effective, we decided on surgical treatment. Bilateral pedicle screws and the smiley face rod method were applied, and both fractures subsequently healed. In the 2 years since the surgery, the patient has returned to sports and has the potential to become a professional player

High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage.

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aβ species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aβ1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aβ1-42 were significantly greater than those of LMW-Aβ1-42. Therapeutic reduction of HMW-Aβ1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage

レゾルシル酸ラクトンLL-Z1640-2の成人T細胞白血病/リンパ腫に対する治療効果

Adult T-cell leukaemia/lymphoma (ATL) remains incurable. The NF-κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF-β-activated kinase 1 (TAK1), an IκB kinase-activating kinase, triggers the activation of NF-κB. The resorcylic acid lactone LL-Z1640-2 is a potent irreversible inhibitor of TAK1/extracellular signal-regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL-Z1640-2 against ATL. LL-Z1640-2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of IRF4 strongly induced ATL cell death while downregulating MYC. LL-Z1640-2 as well as the NF-κB inhibitor BAY11-7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF-κB-IRF4-MYC axis. The treatment with LL-Z1640-2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL-Z1640-2 against IL-2-responsive ATL cells in the presence of IL-2. Therefore, LL-Z1640-2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL-Z1640-2

Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS(SV40)) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS(SV40) in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS(SV40) formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS(SV40) likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS(SV40) can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells

Interaction of RNA with a C-terminal fragment of the amyotrophic lateral sclerosis-associated TDP43 reduces cytotoxicity

A hallmark of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is formation of inclusion bodies (IBs) from misfolded proteins in neuronal cells. TAR RNA/DNA-binding protein 43 kDa (TDP43) is an ALS-causative protein forming IBs in ALS patients. The relation between localization of the IBs and neurotoxicity remains largely unknown. We characterized aggregation of fluorescently tagged TDP43 and its carboxyl-terminal fragments (CTFs) by analytical fluorescence imaging techniques. Quantitative time-lapse analysis in individual live cells showed that fluorescent-protein-tagged TDP43 was cleaved and a 35 kDa TDP43 CTF (TDP35) formed ubiquitin (Ub)-negative cytoplasmic IBs. Although TDP35 formed mildly toxic Ub-negative IBs in the cytoplasm, TDP25, another type of a TDP43 CTF, efficiently formed sufficiently toxic Ub-positive IBs. One-or two-color fluorescence correlation spectroscopy (FCS/FCCS) revealed that coaggregation of TDP25 with TDP43 was initiated by depletion of the RNA that binds to TDP25. Moreover, nuclear localization tagging TDP25 reduced the rate of neuronal cell death. These observations point to the need to elucidate the novel sequestration mechanism and details of the toxicity of the misfolded and aggregation-prone TDP43 CTFs (as well as the RNA binding and nuclear retention) in order to identify possible preventive interventions against ALS

Recurrence of Left Ventricular Outflow Tract Obstruction Requiring Alcohol Septal Ablation after Transcatheter Aortic Valve Implantation

Left ventricular outflow tract (LVOT) obstruction is sometimes observed in patients with severe aortic stenosis (AS). It is still controversial how to manage the remaining severe AS, when LVOT obstruction is well-controlled by medical therapy. We report a case with acute recurrence of LVOT obstruction requiring emergent alcohol septal ablation (ASA) after transcatheter aortic valve implantation (TAVI), even in a stable state on beta-blockers. For the ASA procedure, transesophageal echocardiography was useful to clearly observe the perfusion area of the target septal branch by injecting microbubble contrast. Since it took some time to cause the recurrence of LVOT obstruction in this case, careful evaluation should be done after TAVI in high-risk patients for LVOT obstruction before terminating the TAVI procedure

Colorectal endoscopic submucosal dissection using the water pressure method for diverticulum-associated lesions: A case series study (with video)

Background and study aims Colorectal endoscopic submucosal dissection (ESD) of diverticulum-associated lesions is challenging because these lesions require precise excision in narrow spaces. The water pressure method (WPM) uses active water pressure by the waterjet function under saline solution-filled conditions. This study aimed to determine the feasibility of WPM for resection of diverticulum-associated lesions. Patients and methods This was a retrospective, observational case series study. We reviewed diverticulum-associated lesions treated by ESD with WPM at our institution between June 2017 and July 2021. Diverticulum-associated lesions were classified as follows: type 1, lesions in contact with or within 3 mm of the edge of a diverticulum; type 2, lesions that partially infiltrated the interior of a diverticulum; and type 3, lesions that infiltrated the interior of and completely covered the diverticulum. We collected data on the clinical characteristics and outcomes of the lesions. Results Seven diverticulum-associated lesions were treated with ESD using WPM. The median lesion size was 37 mm (interquartile range: 25–54 mm). There were three cases of type 1, three cases of type 2, and one case of type 3. Three lesions were resected circumventing the diverticulum, and four lesions involved resection of the diverticulum. The en bloc resection and R0 resection rates were 86 %. One patient had severe fibrosis, which caused perforation, and in another patient, the diverticulum was too deep and narrow to be completely isolated. Conclusions WPM allowed for precise procedures in the diverticulum. The feasibility of WPM has been suggested for diverticulum-associated lesions, although cases have been complex