In connection with our studies on antibacterial active compounds in the class of new oxazolidinones against Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) strains, some ...molecular modifications were attempted. In this study, molecular modifications of 4‐aminomethyloxazolidin‐2‐ones (3a) to the corresponding 4‐acylaminomethyloxazolidin‐2‐one derivatives (3c–d) and preparations of the represented twin‐drug type molecules (10–14) were investigated. Some additional 4‐dialkylaminomethyloxazolidin‐2‐ones (2) were also synthesized. The synthesized compounds were evaluated for antibacterial activity with Gram‐positive (S. aureus) and Gram‐negative (E. coli) strains.
The cell-cycle transition from G
1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically ...encoded fluorescent probes for this purpose. These probes effectively label individual G
1 phase nuclei red and those in S/G
2/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.
In connection with our studies on hydantoin derivatives, a conventional regioselective chemical transformation of 5-methylene hydantoins 4a–c to 5-aminomethyl-substituted hydantoins 5–10 or to ...5-amino-5-methyl-disubstituted hydantoins 11–14 is described. Synthesis of bivalent twin-drug type hydantoin derivatives 19–24 and the binding property of a bivalent symmetrical hydantoin derivative 24b to sulfated glycosaminoglycans are also described.
The condition of arteriovenous fistula (AVF) blood flow is typically checked by using auscultation; however, auscultation should require a qualitative judgment dependent on the skills of doctors, and ...further attention to contact infection is required. For these reasons, this study developed a non-contact and non-invasive medical device to measure the pulse wave of AVFs by applying optical imaging technology. As a first step toward realization of the quantification judgment based on non-contact AVF measurement, we experimentally validated the developed system, whereby the hemodynamics of 168 subjects were visually and quantitatively evaluated based on clinical tests. Based on the evaluation results, the fundamental statistical characteristics of the non-contact measurement, including the average and median values, and distribution of measured signal-to-noise power ratio, were demonstrated. The clinical test results contributed to the future construction of quantified criteria for the AVF condition with the non-contact measurement.
This study examined the hypoglycaemic activity of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) in ICR mice by oral glucose tolerance testing. The blood glucose level was significantly lower ...in the C. paliurus extract treatment group than in the control group after animals were given sucrose. This difference was not observed following the administration of glucose. We demonstrated that the chronological change in the level of blood glucose in genetically hyperglycemic obese KK-A
y
mice is significantly lower when C. paliurus extract is administered daily for three weeks. An in vitro study showed that C. paliurus inhibits α-glucosidase, a disaccharide-degrading enzyme in the small intestinal mucosa, leading to a decrease in the absorption of glucose into the blood and a subsequent lowering of the blood glucose level.
In Xenopus laevis, sperm-egg interaction promotes partial proteolysis and/or tyrosine phosphorylation of uroplakin III (UPIII) and the tyrosine kinase Src, which both localize to the ...cholesterol-enriched egg membrane microdomains (MDs). Here we show that sperm promote proteolysis and/or tyrosine phosphorylation of UPIII and Src in MDs isolated from ovulated and unfertilized eggs (UF-MDs). An antibody against the extracellular domain of UPIII interferes with these events. Inhibition of fertilization by anti-UPIII antibody is rescued by co-incubation with UF-MDs. This suggests that, like MDs in intact eggs, the isolated UF-MDs are capable of interacting with sperm, an interaction that does not interfere with normal fertilization but rather augments the ability of sperm to fertilize eggs pretreated with anti-UPIII antibody. This unexpected effect of UF-MDs on sperm requires UPIII function in UF-MDs and protein kinase activity in sperm. MDs isolated from progesterone-treated mature oocytes, but not ovarian immature oocytes, are similarly functional as UF-MDs. The anti-UPIII extracellular domain antibody binds more effectively to the surface of mature than immature ovarian oocytes. We propose that the structural and functional competency of the UPIII-Src signaling system in MDs is strictly regulated during oocyte maturation and subsequently in sperm-mediated egg activation and fertilization. The fertilization-related signaling properties seen in UF-MDs can be partially reconstituted in MDs of human embryonic kidney 293 cells (293-MDs) expressing UPIII, Src and uroplakin Ib. However, 293-MDs expressing a proteolysis-resistant mutant of UPIII are less functional, suggesting that the availability of UPIII to protease action is important for MD function.
Abstract
Background
Etelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety ...and efficacy of replacing cinacalcet with etelcalcetide in HD patients.
Methods
One hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively.
Results
Of the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (
p
< 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients,
p
= 0.087; 90 patients,
p
< 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed.
Conclusions
This study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet.
Trial registration
UMIN,
UMIN000027637
; Registered on June 5, 2017.
Aim
To clarify the prevalence and degree of maternal microchimerism in Japanese children with type 1 diabetes, as well as its effect on phenotypic variation.
Methods
We studied 153 Japanese children ...with type 1 diabetes, including 124 children positive for β‐cell autoantibodies, and their 71 unaffected siblings. The number of circulating microchimeric cells per 105 host cells was estimated by the use of quantitative‐polymerase chain reaction targeting non‐transmitted maternal human leukocyte antigen alleles. The results were compared to previous data from white European people. Phenotypic comparison was performed between maternal microchimerism carriers and non‐carriers with diabetes.
Results
Maternal microchimerism was detected in 15% of children with autoantibody‐positive type 1 diabetes, 28% of children with autoantibody‐negative type 1 diabetes, and 16% of unaffected siblings. There were no differences in the prevalence or levels of maternal microchimerism among the three groups or between the children with type 1 diabetes and their unaffected siblings. Furthermore, maternal microchimerism carriers and non‐carriers exhibited similar phenotypes.
Conclusions
Maternal microchimerism appears to be less common in Japanese children with type 1 diabetes than in white European people. Our data indicate that maternal microchimerism is unlikely to be a major trigger or a phenotypic determinant of type 1 diabetes in Japanese children and that the biological significance of maternal microchimerism in type 1 diabetes may differ among ethnic groups.
What's new?
Maternal microchimerism appears to be less common in Japanese children with type 1 diabetes than in white European people with this condition.
Circulating microchimeric cells are unlikely to be a major trigger or a phenotypic determinant of type 1 diabetes in Japanese children.
The biological significance of maternal microchimerism in type 1 diabetes may differ among ethnic groups.
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