The impact of sarcopenia on short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer

Journal of Gastroenterology - Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes...     

Possible Cerebral Vasculitis in a Case with Rheumatoid Arthritis

Cerebral rheumatoid vasculitis (CRV) is a rare, fatal, and diagnostically challenging disorder. We herein report an 81-year-old woman with a 4-year history of rheumatoid arthritis who presented with a fever, progressive disturbance of consciousness, high level of rheumatoid factor, and hypocomplementemia. The enhancement of the perforating branches in the left middle cerebral artery led us to suspect CRV. A brain biopsy could not be performed. After we intensified steroid therapy, the size of the cerebral lesions temporarily decreased. However, recurrence in the left frontal lobe occurred one month later, and the patient subsequently died. Early intensive treatments may be needed for CRV.     

Angioscopic assessments and clinical outcomes one year after polymer-free biolimus A9-coated coronary stent implantation

BackgroundPolymer-free biolimus A9-coated coronary stent (DCS) has novel features which lead to the expectation of better arterial healing. However, comparisons of intravascular status between DCS and drug-eluting stents (DES), and robust real-word clinical assessments of DCS have been lacking to date.MethodsFrom September 2017 to September 2018, we evaluated the intra-vascular status of 74 DCS implanted in 55 lesions from 43 patients using coronary angioscopy (CAS) approximately one year after implantation from a cohort of 219 lesions in 158 patients. We set 239 second-generation durable-polymer DES (DP-DES) implanted in 211 lesions from 180 patients from a cohort of 2652 lesions in 1914 patients as the control. Angioscopic images were analyzed to determine (1) the dominant degree of neointimal coverage (NIC) over the stent; (2) the heterogeneity of NIC; (3) yellow color grade of the stented segment; and (4) the presence of intra-stent thrombus. The primary outcome was the incidence of thrombus and secondary outcomes were the other CAS findings, and the 1-year clinical outcomes which included target lesion revascularization (TLR) and major adverse cardiac events (MACE). To minimize inter-group differences in baseline characteristics, propensity score matching was performed for clinical outcomes.ResultsIncidence of thrombus adhesion was similar in DCS and DP-DES groups (28.4% versus 22.6%, p = 0.31). However, the dominant NIC grade was significantly higher in DCS (p < 0.001), while NIC was more heterogeneous in DCS than in DP-DES (p = 0.001). Maximum yellow color grade was similar (p = 0.22). After propensity score matching, 202 lesion pairs from 146 patient pairs were retained for analysis. The cumulative incidence of TLR (4.6% versus 3.8%, p = 0.38) and MACE (11.6% versus 11.7%, p = 0.84) was similar for DCS and DP-DES.ConclusionsDCS showed thrombus adhesion and clinical outcomes at 1 year similar to DP-DES. DCS can thus be used with similar safety and efficacy as DP-DES.     

Melatonin binding sites in estrogen receptor-positive cells derived from human endometrial cancer

Our previous work showed that melatonin (N-acetyl-5-methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor-positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2-[125I]-iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm (similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2-[125I]-iodomelatonin at all concentrations tested (10(-8) to 10(-4) m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.     

Anandamide induces necrosis in primary hepatic stellate cells

The endogenous cannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces apoptosis in many cell types. Although AEA levels are elevated in liver fibrosis, its role in fibrogenesis remains unclear. This study investigated effects of AEA in primary hepatic stellate cells (HSCs). Anandamide blocked HSC proliferation at concentrations of 1 to 10 micromol/L but did not affect HSC proliferation or activation at nanomolar concentrations. At higher concentrations (25-100 micromol/L), AEA rapidly and dose-dependently induced cell death in primary culture-activated and in vivo-activated HSCs, with over 70% cell death after 4 hours at 25 micromol/L. In contrast to treatment with Fas ligand or gliotoxin, AEA-mediated death was caspase independent and showed typical features of necrosis such as rapid adenosine triphosphate depletion and propidium iodide uptake. Anandamide-induced reactive oxygen species (ROS) formation, and an increase in intracellular Ca(2+). Pretreatment with the antioxidant glutathione or Ca(2+)-chelation attenuated AEA-induced cell death. Although the putative endocannabinoid receptors CB1, CB2, and VR1 were expressed in HSCs, specific receptor blockade failed to block cell death. Depletion of membrane cholesterol by methyl-beta-cyclodextrin inhibited AEA binding, blocked ROS formation and intracellular Ca(2+)-increase, and prevented cell death. In primary hepatocytes, AEA showed significantly lower binding and failed to induce cell death even after prolonged treatment. In conclusion, AEA efficiently induces necrosis in activated HSCs, an effect that depends on membrane cholesterol and a subsequent increase in intracellular Ca(2+) and ROS. The anti-proliferative effects and the selective killing of HSCs, but not hepatocytes, indicate that AEA may be used as a potential anti-fibrogenic tool.     

Direct demonstration of the cross-bridge recovery stroke in muscle thick filaments in aqueous solution by using the hydration chamber

Despite >50 years of research work since the discovery of sliding filament mechanism in muscle contraction, structural details of the coupling of cyclic cross-bridge movement to ATP hydrolysis are not yet fully understood. An example would be whether lever arm tilting on the myosin filament backbone will occur in the absence of actin. The most direct way to elucidate such movement is to record ATP-induced cross-bridge movement in hydrated thick filaments. Using the hydration chamber, with which biological specimens can be kept in an aqueous environment in an electron microscope, we have succeeded in recording ATP-induced cross-bridge movement in hydrated thick filaments consisting of rabbit skeletal muscle myosin, with gold position markers attached to the cross-bridges. The position of individual cross-bridges did not change appreciably with time in the absence of ATP, indicating stability of time-averaged cross-bridge mean position. On application of ATP, individual cross-bridges moved nearly parallel to the filament long axis. The amplitude of the ATP-induced cross-bridge movement showed a peak at 5–7.5 nm. At both sides of the filament bare region, across which the cross-bridge polarity was reversed, the cross-bridges were found to move away from, but not toward, the bare region. Application of ADP produced no appreciable cross-bridge movement. Because ATP reacts rapidly with the cross-bridges (M) to form complex (M·ADP·Pi) with an average lifetime >10 s, the observed cross-bridge movement is associated with reaction, M + ATP → M·ADP·Pi. The cross-bridges were observed to return to their initial position after exhaustion of ATP. These results constitute direct demonstration of the cross-bridge recovery stroke.     

Detection of BCL2-IGH rearrangement on paraffin-embedded tissue sections obtained from a small submucosal tumor of the rectum in a patient with recurrent follicular lymphoma

A 59-year-old woman was admitted to our hospital because of recurrent follicular lymphorna (FL). Colonoscopic examination revealed a rectal submucosal tumor (SMT) without any erosions and ulcers. In this patient, it was difficult to distinguish non-Hodgkin‘s lymphoma (NHL) invasion from other disorders of the colon including carcinoid tumor merely based on endoscopic findings. Histopathologic and immunohistochemical studies on biopsy specimens showed an infiltration of atypical lymphocytes that were positive for CD20 and BCL2 but negative for UCHL-1. Fluorescence in situ hybridization on paraffin-embedded tissue sections (T-FISH) identified a translocation of BCL2 with IGHgene.Based on these findings, the tumor was defined as an invasion of FL. T-FISH method is useful for the detection of a monoclonality of atypical lymphocytes in an SMT of the gastrointestinal tract, and particularly for the detection of chromosomal translocations specific to lymphoma subtypes.