Asymmetric Synthesis of α‐Amino Phosphonic Acids using Stable Imino Phosphonate as a Universal Precursor

A practical method for synthesizing chiral α-amino phosphonic acid derivatives was developed. Readily available and stable N-o-nitrophenylsulfenyl (Nps) imino phosphonate was utilized as a substrate for a highly enantioselective Friedel–Crafts-type addition of indole or pyrrole nucleophiles catalyzed by chiral phosphoric acid. The resulting adduct was easily converted to N-9-fluorenylmethyloxycarbonyl (Fmoc) amino phosphonic acid, which is useful for synthesizing peptides containing an amino phosphonic acid

Comparison of Conventional 2D CC (Cranio-Caudal) + MLO (Medio-Lateral Oblique) Bi-Directional Photography and 2D-MLO + DBT-MLO (Digital Breast Tomosynthesis) in Mammography Examination

Introduction: Mammography (MMG) is an excellent examination for breast cancer detection and is widely used in both screening and clinical practice. However, the breast thickness and background the concentration of the mammary gland is large among individuals, and the mammary gland and cancer may overlap and it may not be possible to point out a lesion. In recent years, digital breast tomosynthesis (hereinafter referred to as DBT) has been introduced to solve these problems, and its usefulness has been reported in clinical practice. Therefore, in anticipation of a higher cancer detection rate etc., we compared the conventional 2D CC + MLO 2-way MMG examination with 2DMLO + DBTMLO 2-way MMG examination.Materials and Methods: The combination of 2D CC + MLO and 2DMLO + DBTMLO was read for 95 cases of breast cancer taking 2D CC and MLO and DBT MLO from May 2016 to October 2017. It was judged that the category 3 or more required detailed examination, cancer detection, and cancer detection rates were compared. Subjects were 28 to 87 years of age (median: 55 years), breast composition: high concentration 15.8% (15 cases), heterogeneous high concentration 47.4% (45 cases), mammary gland 28.4% (27 cases), Fatty was 8.4% (8 cases).Results: The cancer detection rate was 87% for the 2D CC + MLO combination and 94% for the 2DMLO + DBTMLO combination in 95 cases of breast cancer. The interpretation time was 95 minutes for the 2D CC + MLO combination and 110 minutes for the 2DMLO + DBTMLO combination.The breast cancer detected only by the combination of 2D CC + MLO was scattered in 1 case and was classified as Category 3 by FAD. Breast cancer detected only by the combination of 2DMLO + DBTMLO: 8 cases with uneven distribution of breast composition, 3 cases with scattered mammary gland, 3 cases with 5 cases with disordered construction, Category 4 with 3 cases with FAD was.Conclusion: Both 2D CC + MLO combination and 2DMLO + DBTMLO combination are considered useful for screening MMG examination. In particular, we would like to consider the introduction to medical examinations for the addition of MMG in DBT, but the issue of the amount of image information, the problem of exposure to radiation, the direction of imaging, the establishment of interpretation methods etc. are future issues

Micro-patterned culture of iPSC-derived alveolar and airway cells distinguishes SARS-CoV-2 variants.

iPS細胞から作った肺胞や気道の細胞によりSARS-CoV-2変異株の病原性を比較評価する. 京都大学プレスリリース. 2024-03-29.Micro-patterning a new system to induce alveolar and airway epithelial cells. 京都大学プレスリリース. 2024-03-29.The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are their entry points; however, in addition to their limited source, the culture of human alveolar epithelial cells is especially complicated. Induced pluripotent stem cells (iPSCs) are an alternative source of human primary stem cells. Here, we report a model for distinguishing SARS-CoV-2 variants at high resolution, using separately induced iPSC-derived alveolar and airway cells in micro-patterned culture plates. The position-specific signals induced the apical-out alveolar type 2 and multiciliated airway cells at the periphery and center of the colonies, respectively. The infection studies in each lineage enabled profiling of the pathogenesis of SARS-CoV-2 variants: infection efficiency, tropism to alveolar and airway lineages, and their responses. These results indicate that this culture system is suitable for predicting the pathogenesis of emergent SARS-CoV-2 variants

Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles

初期化を阻害する転写因子が分化を促進する. 京都大学プレスリリース. 2013-04-02.Transcription factors (TFs) are able to regulate differentiation-related processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation

THYROID DYSFUNCTION FOLLOWING ALPHA-INTERFERON TREATMENT FOR CHRONIC HEPATITIS C

In order to evaluate the influnces of IFNα on thyroid function, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4, tri-iodothyronine (T3), and thyroxine-binding globulin were examined in IFNα-treated 351 patients with chronic hepatitis C before and during therapy. As therapy, either 3 million units (MU) of human lymphoblastoid IFNα or 9MU of recombinant IFNα2a was administrated daily for the initial two weeks followed by three times a week for 22 weeks. There were nine patients showing thyroid dysfunction during IFNα therapy. They consist of one relapse of Graves' disease, one relapse of Hashimoto thyroiditis, one development of apparent thyroid insufficiency from subclinical hypothyroidism, five cases with transient hyperthyroidism and one case with transient hypothyroidism. T4 and T3 levels in most patients who transiently developed thyroid dysfunction were normalized spontaneously after the discontinuation of IFNα. Thyroid-related autoantibodies were positive in 4 patients before IFNα therapy and newly developed in one patient during therapy. Attention should be paid first to the previous histories of autoimmune thyroid diseases and the existence of thyroid-related autoantibodies for the prediction of development of thyroid dysfunction during IFNα therapy. In addition, serial examinations of TSH, T3 and T4 should be also necessary for early detection of transient thyroid dysfunction during IFNα therapy

Long-term perospirone treatment with a single dose at bedtime in schizophrenia : relevant to intermittent dopamine D2 receptor antagonism

Perospirone, a serotonin 5-HT2A and dopamine D2 receptor antagonist, is metabolized to ID-15036 by CYP3A4 and the elimination half-life (T1/2) for the latter is longer than the former. The active metabolite ID-15036 is an 8-times weaker D2 antagonist than perospirone, although it has a high affinity for 5-HT2A receptor. In this study, we measured the plasma concentrations of peospirone and ID-15036 in the long-term stable schizophrenic patients with a single dose of perospirone at bedtime. The mean level of perospirone at 11-15 hrs after a last dosing was much lower (0.49 ng/ml) than that of ID-15036 (2.89 ng/ml). These results show that a long-term perospirone monotherapy with a single dose at bedtime is effective for the maintenance treatment of chronic schizophrenia and also suggest the possibility that intermittent D2 receptor blockade may be sufficient for effective relapse prevention

Effect of carbamazepine on the single oral dose pharmacokinetics of perospirone and its active metabolite

Perospirone is a serotonin 5-HT2A and dopamine D2 receptor antagonist which originated in Japan. It has been shown that perospirone is metabolized to ID-15036 mainly by CYP3A4 based on an in vitro study. To investigate the metabolism of perospirone in humans, the authors measured the concentration of perospirone and ID-15036 after a single oral dose of perospirone (8 mg) in 10 healthy male subjects, before and during coadministration of carbamazepine, known as a potent inducer of CYP3A4. Before carbamazepine coadministration, the peak plasma concentrations ± SD of perospirone and ID-15036 were 4.0 ± 4.3 and 11.7 ± 7.1 ng/ml, respectively. During carbamazepine coadministration, the concentration of perospirone was decreased below the detection limit, and that of ID-15036 was 6.0 ± 1.7 ng/ml. The concentrations of perospirone and ID-15036 were influenced significantly by the treatment with carbamazepine, and this was probably attributable to the induction of CYP3A4. This study provided an in vivo evidence of involvement of CYP3A4 in the metabolism of perospirone

Comparing Transition Procedures in Modified Simulated-Annealing-Based Synthetic Reconstruction Method without Samples

In this paper, we modify a synthetic reconstruction (SR) method without samples. The synthetic reconstruction method is a method to generate attributes of population such as age, sex and kinship within a family according to available statistics. Although the original SR method employs some individual samples that are collected to make a statistics, it is criticized that generated attributes are only within the samples used in the reconstruction process. In this paper, we employ a simulated annealing-based SR method without samples. We compare two types of generation methods of a candidate solution in a search of simulated annealing: changing age of an agent (age-change) or swapping ages of two agents (age-swap). Results of synthetic reconstruction show that age-change is better when we limit the number of search. On the other hand, age-swap is better when we have enough number of search for reconstructing a population