Effects of bilateral anodal transcranial direct current stimulation over the tongue primary motor cortex on cortical excitability of the tongue and tongue motor functions.

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Drosophila Strip serves as a platform for early endosome organization during axon elongation

Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.This work was supported by grants from the National Institute of General Medical Science of the National Institutes of Health (R01-GM085232 to V.I.G.), the National Institutes of Health (R01-DC005982 to L.L.), the Japanese Ministry of Education, Science, Sports, Culture, and Technology (MEXT), the Japan Society for the Promotion of Science, and the Japan Science and Technology Agency (to C.S., K.T., Y.Y., M.M., and T.C.)

Retroperitoneal hemorrhage with COVID-19

Introduction: Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported. Case Presentation : A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia. Conclusion : When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient’s condition

Long-Term Outcome of Proton Therapy and Carbon-Ion Therapy for Large (T2a–T2bN0M0) Non–Small-Cell Lung Cancer

IntroductionAlthough many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non–small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification.MethodsFrom April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0.ResultsThe median follow-up period for living patients was 51 months (range, 24–103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients.ConclusionParticle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible

Effect of heart rate and myocardial contractile force on coronary resistance.

The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pressure. The changes in mean coronary resistance showed a significant linear relationship to changes in developed tension. The changes in coronary resistance caused by varying the heart rate and contractile force were so small that a normal coronary vascular tree could easily compensate for the increase in resistance. However, it is supposed that with critical stenosis of the vascular tree even a small increase in resistance might cause deleterious effects on coronary blood flow.</p

Expansion of a CD28-Intermediate Subset among CD8 T Cells in Patients with Infectious Mononucleosis

Infectious mononucleosis (IM) is an acute sporadic infection that usually affects young adults, and during infection a massive expansion of CD8 T cells is generally considered to occur. However, CD28 expression of the expanded cells has not been characterized. When peripheral blood mononuclear cells of acute IM (AIM) patients were analyzed by flow cytometry, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28 negative, intermediate (int), and positive, was seen for CD8 T cells. We studied 26 IM patients who were diagnosed on the basis of standard methods and found that all patients had the continuous CD28 spectrum. CD28 is a costimulatory molecule on T cells, and its expression is associated with the subdivision of CD8 cells into cytotoxic (CD28-positive) and suppressor (CD28-negative) T cells. After 24 h of ex vivo culturing, however, the continuous spectrum was found to consist of only CD28-positive and CD28-negative CD8 T cells, because the CD28-int cells had disappeared due to apoptosis. The CD28-int T cells have several cytotoxic functions, suggesting that CD28-int T cells are effectors. Examination of other costimulatory markers in AIM patients showed that CD80 and CD152 were not affected. In patients with other viral infections, such as measles or rubella, however, the continuous spectrum was not detected. These results suggest that there is an unusual CD28 expression pattern in patients with AIM, namely, the presence of a functional CD28-int subset among CD8 T cells. These findings are of special importance for clarifying the defense mechanism against Epstein-Barr virus infection, and the role of CD28 molecules in humans and should also be helpful for the diagnosis of AIM

Semisynthesis of Complex-Type Biantennary Oligosaccharides Containing Lactosamine Repeating Units from a Biantennary Oligosaccharide Isolated from a Natural Source

Poly-<i>N</i>-acetyllactosamine (poly-LacNAc) structures on glycoproteins play important roles in essential biological events such as cell–cell adhesion. Here, we report a new strategy for the semisynthesis of LacNAc-extended complex-type biantennary oligosaccharides. We found an efficient isopropylidenation reaction that selectively protects the terminal Gal-3,4-OH of a biantennary complex-type nonasaccharide isolated from a natural source. This finding enabled the conversion of the nonasaccharide into the two types of oligosaccharides containing di-LacNAc units at one or two antennae via ten-step chemical sequences