Search

α-Tomatine is a steroidal glycoalkaloid in tomato plants and degrades with ripening. The aglycone form, tomatidine, is reported to have beneficial effects. In this study, the ability of food-related microorganisms to produce tomatidine from α-tomatine was evaluated. A total of 11 strains of Aspergillusspecies belonging to the section Nigriexhibited tomatinase activity, and Aspergillus luchuensisJCM 22302 was selected for optimization due to its high activity in its mycelia, conidia, and non-mycotoxin-producing property. Next, using A. luchuensisJCM22302 conidia, the highest yield was obtained in a 24-h reaction with 50 m mof acetic acid–sodium acetate buffer (pH 5.5) at 37 °C. Similar to the tomato pathogen Fusarium oxysporum f. lyceopersici, the time course analysis suggested that A. luchuensisJCM 22302 removed the entire sugar moiety in a single step. Future research will focus on utilizing conidia for large-scale tomatidine production because of their high tolerance and manageability.Graphical AbstractBlack koji was found to contain tomatinase activity. It was implied that A. luchuensisJCM22302 removed the whole sugar moiety of α-tomatine.

Eine Interstitielle Lungenerkrankung (interstitial lung disease, ILD) ist ein schwerwiegendes und lebensbedrohendes unerwünschtes Ereignis in der Behandlung von Lungenkrebs. Nab-PTX (an Albumin-Nanopartikel gebundenes Paclitaxel) ist eine neuartige, lösungsmittelfreie Formulierung von Paclitaxel (PTX). Die Inzidenz der nab-PTX-induzierten ILD ist zwar nicht bekannt, man geht jedoch davon aus, dass diese Formulierung mit einem vergleichbaren ILD-Risiko verbunden ist wie PTX. Wir berichten hier über 3 Patienten, die nach der Behandlung mit nab-PTX eine schwere ILD entwickelten. Wir unterstreichen damit das Risiko für das Auftreten einer medikamenteninduzierten ILD nach einer nab-PTX-Therapie und heben hervor, dass diese neue Formulierung in Bezug auf das ILD-Risiko möglicherweise weniger sicher ist als PTX. Übersetzung aus Case Rep Oncol 2017;10:683-688 (DOI: 10.1159/000479148).

Osimertinib may be effective in treating CNS metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients with previously treated (T790M cohort) and untreated patients (first-line cohort) with EGFRmutation. Here we reported the results of first-line cohort.

When insulin treatment is started in patients with type 2 diabetes mellitus (T2DM), there are many regimens that control serum glucose levels to a normal range. Basal-bolus insulin therapy is one of the most effective treatments for improving glycemic control to prevent the progression of diabetic microvascular complications. This study was conducted to determine whether step-up insulin treatment with premixed insulin aspart-30/70 (BIAsp 30) or lispro-50/50 (Mix50) in Japanese patients with type 2 diabetes mellitus could achieve better glycemic control. In this open label study, 72 insulin-naïve patients with poorly controlled T2DM (HbA1c ≥8.4%), who had been taking oral antidiabetic drugs for at least 12 months, were randomized to receive BIAsp 30 or Mix50 therapy. Patients started treatment of a pre-dinner injection of each type of insulin (Step 1). At 16 ± 2 weeks, a pre-breakfast injection of each type of insulin was added if HbA1c exceeded 7.4% (step 2). If patients had still not achieved HbA1c <7.4% after an additional 16 ± 2 weeks, a pre-lunch insulin injection was added (step 3). Hypoglycemic episodes were also recorded. The cumulative percentages of subjects who achieved HbA1c <7.4% were 36.1% (13/36) for both Mix50 and BIAsp 30 in step 1, 62.9% (23/36) for BIAsp 30 and 52.8% (19/36) for Mix50 in step 2, and 66.7% (24/36) in BIAsp 30 and 72.2% (26/36) in Mix50 in step 3. The achievement rates of HbA1c <7.4% were not statistically different between the two groups. A total of ten hypoglycemic episodes occurred in this study. However, there were no severe hypoglycemic episodes. All cases recovered by taking glucose and drinking juice. Mix50 step-up treatment has a clinical effect in achieving good glycemic control equal to that of BIAsp 30 treatment.

We developed a novel technique for manipulating the activity of transcription factors with blue light (termed “PICCORO”) using the bacterial BLUF-type photoreceptor protein PixD. The chimeric dominant-negative T-box transcription factor No Tail formed heterologous complexes with a PixD decamer in a light-dependent manner, and these complexes affected transcription repressor activity. When applied to zebrafish embryos, PICCORO permitted regulation of the activity of the mutant No Tail in response to 472-nm light provided by a light-emitting diode.

The objective of this study was to determine how age and psychological characteristics assessed prior to diagnosis could predict psychological distress in outpatients immediately after disclosure of their diagnosis.

Ascidians are among the most distant chordate relatives of the vertebrates. However, ascidians share many features with vertebrates including a notochord and hollow dorsal nerve cord. A screen for N-ethyl-N-nitrosourea (ENU)-induced mutations affecting early development in the ascidian Ciona savignyi resulted in the isolation of a number of mutants including the complementing notochord mutants chongmague and chobi. In chongmague embryos the notochord fails to develop, and the notochord cells instead adopt a mesenchyme-like fate. The failure of notochord development in chongmague embryos results in a severe truncation of tail, although development of the tail muscles and caudal nerve tracts appears largely normal. Chobi embryos also have a truncation of the tail stemming from a disruption of the notochord. However, in chobi embryos the early development of the notochord appears normal and defects occur later as the notochord attempts to extend and direct elongation of the tail. We find in chobi tailbud embryos that the notochord is often bent, with cells clumped together, rather than extended as a column. These results provide new information on the function and development of the ascidian notochord. In addition, the results demonstrate how the unique features of ascidians can be used in genetic analysis of morphogenesis.

The tadpole larva of solitary ascidians has 40 notochord cells in its tail. Of these cells, 32 in the anterior and middle part of the tail are derived from the A-line blastomeres, while 8 in the posterior part of the tail originate from the B-line blastomeres. Previous experiments involving continuous dissociation of daughter blastomeres from the first cleavage to the 110-cell stage suggested that cellular interactions may be involved in the formation of notochord cells. In the present study, the presumptive-notochord blastomeres isolated from the 32-cell embryos did not develop features of notochord. These results suggest that cellular interactions may be required for the fate specification of notochord, that is to say, notochord formation occurs as a result of inductive interaction between blastomeres. In order to confirm the involvement of induction in the determination of notochord and to identify the inducer blastomeres, the presumptive-notochord blastomeres at the 32-cell stage were coisolated or recombined with one of the surrounding blastomeres in a series of experiments. The results suggested that, for the A-line precursors, notochord differentiation occurs as the result of an inductive influence from vegetal blastomeres that include the presumptive-endoderm blastomeres and the presumptive-notochord blastomeres themselves. It was also suggested that induction of notochord is complete by the 64-cell stage and that inductive interactions have to be initiated before the decompaction of blastomeres during the 32-cell stage. Ascidians are Urochordata and are closely related to vertebrates. In vertebrates, it is well known that inductive interactions play a crucial role in the determination of notochord. It appears, therefore, that induction of notochord is common throughout the phylum Chordata.

The tadpole larva of an ascidian develops 40 notochord cells in the center of its tail. Most of the notochord cells originate from the A-line precursors, among which inductive interactions are required for the subsequent differentiation of notochord. The presumptive-endoderm blastomeres or presumptive-notochord blastomeres themselves are inducers of notochord formation. Notochord induction takes place during the 32-cell stage. In amphibia, mesoderm induction is thought to be mediated by several growth factors, for example, activins and basic fibroblast growth factor (bFGF). In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promoted the formation of notochord at a low concentration of bFGF (0.02 ng/ml), while activin failed to induce notochord differentiation. The effect of bFGF reached a maximum at the end of the 32-cell stage and rapidly faded at the beginning of the subsequent cleavage, the time for full induction of notochord being at least 20 minutes. The expression of As-T, a previously isolated ascidian homolog of the mouse Brachyury (T) gene, starts at the 64cell stage and is detectable exclusively in the presumptivenotochord blastomeres. The present study showed that presumptive-notochord blastomeres, isolated at the early 32-cell stage, neither differentiated into notochord nor expressed the As-T gene. However, when the presumptivenotochord blastomeres were coisolated or recombined with inducer blastomeres, transcripts of As-T were detected. When presumptive-notochord blastomeres were treated with bFGF, the expression of the As-T gene was also detected. These results suggest that inductive interaction is required for the expression of the As-T gene and that the expression of the As-T gene is closely correlated with the determined state of the notochord-precursor cells.

Osimertinib has been reported to be effective against central nervous system (CNS) metastasis from activating EGFRmutation-positive NSCLC. Nevertheless, the true antitumor effects of osimertinib alone for CNS metastasis are unclear because the aforementioned studies included previously irradiated cases, in which tumor shrinkage can occur later owing to the effects of radiotherapy (RT). This study aimed to evaluate the efficacy of osimertinib against RT-naive CNS metastasis from sensitizing EGFRmutation-positive NSCLC.

Introduction:Abnormal activation states of leukocytes and leukocyte-platelet-interactions play key roles in organ injury induced by atherosclerotic disease, diabetes mellitus, and other inflammatory conditions. However, clinically feasible methods for determining leukocyte activation and the hemorheological character of blood, a non-Newtonian fluid, are limited.Hypothesis:This study reports a novel method for assessment of leukocyte rheological activation with a new designed microchannel array chip to mimic the human microvascular network for microchannel array flow analysis (MCFAN).Methods:Study subjects were 79 healthy volunteers and 42 patients with type 2 diabetes mellitus (DM) and 36 patients with acute coronary syndrome (ACS). By using the anticoagulants heparin and ethylene-diamine-tetraacetic acid (EDTA)-2Na which inhibits platelets and leukocytes by chelating Ca++, we were able to quantify leukocyte rheological activation by the subtraction of passage time of blood treated with both heparin and EDTA-2Na from that of blood treated with heparin only.Results:We confirmed that passage times of whole blood with heparin + EDTA-2Na were always shorter than those of whole blood with only heparin in healthy subjects and patients with DM or ACS under suction pressures of -30 cmH2O. There was a significant correlation between delta whole blood passage time {(heparin tube) - (EDTA-2Na + heparin)} and serum levels of myeloperoxidase and adhesive leukocyte number, respectively, even in blood from patients with DM or ACS, who suffered from inflammation.Conclusions:We have developed a clinically feasible method for assessing leukocyte rheological activation in whole blood in ex vivo.

Background and aim:Left ventricular (LV) diastolic mitral valve regurgitation (dMR) had been reported in patients with severe aortic regurgitation and atrioventricular block, but not in LV aneurysm, a mechanical complication of myocardial infarction (MI). We have recently reported that five patients with LV aneurysm showed dMR and four out of the five died due to heart failure within 6 months. Surprisingly all the five patients showed impaired relaxation (E/A<1) pattern in trance mitral flow despite of high LV end-diastolic pressure. Aims are to explore vortex in LV aneurysm and relative intra LV pressure during early diastole by Vector Flow Mapping (VFM) in patients with LV aneurysm.Method:Study subjects were consecutive 20 LV aneurysmal anterior MI patients and 20 healthy men as control. Exclusion criteria are moderate or severe aortic regurgitation, atrioventricular block, ventricle pacing patients, atrial fibrillation. Study design was a single center observational study. All subjects underwent echocardiography by HITACHI Aloka Lisendo 880. Cardiac catheterization was also performed to the 20 patients with LV aneurysmal anterior MI.Results:We detected a slow flow from the apical aneurysm to the mitral valve during the very late systole to very early diastole (figure A) in 7 out of the 20 LV aneurysmal anterior MI patients and not in the control. Relative intra LV pressure by VFM during early diastole revealed that the pressure in the apex was lower than that of the center of LV in healthy men (figure B), however the opposite in the patients with LV aneurysm (figure C). 7 patients out of the 20 LV aneurysmal anterior MI patients showed dMR and impaired relaxation pattern in TMF. The pressure inversion phenomenon in LV during early diastole in patients with LV aneurysm may modify early diastolic LV inflow.Conclusion:dMR with LV aneurysm, a sign of the poor prognosis, may be due to pressure inversion phenomenon in LV during early diastolic phase.