Tumor-to-tumor metastasis: lung cancer within a thymoma.

Tumor-to-tumor metastasis is a rare phenomenon. We present a rare case of an 83-year-old man with pulmonary squamous cell carcinoma and thymoma. Thymectomy and superior segmentectomy of the left lower lobe were successfully performed on the patient. This thymoma had a region of lung cancer. Metastasis from other tumors to thymoma is rare, and we found a report that described a pancreatic carcinoma metastasizing to thymoma. We report an extremely rare case of metastasis from lung cancer to a thymoma.

Quantitative Modeling and Simulation in PMDA: A Japanese Regulatory Perspective.

In Japan in October 2016, the Pharmaceuticals and Medical Devices Agency (PMDA) began to receive electronic data in new drug applications (NDAs). These electronic data are useful to conduct regulatory assessment of sponsors' submissions and contribute to the PMDA's research. In this article, we summarize the number of submissions of quantitative modeling and simulation (M&S) documents in NDAs in Japan, and we describe our current thinking and activities about quantitative M&S in PMDA.

Analysis of transcriptional control elements in the 5'-upstream region of ovine interferon-tau gene using feeder-independent caprine trophoblast cell line, HTS-1.

Interferon-tau (IFNtau) is a protein secreted from the embryonic trophectoderm of ruminant ungulates during peri-implantation period. This protein acts on the uterine endometrium, which indirectly maintains corpus luteum function, and is therefore considered essential for the process of maternal recognition of pregnancy. Transcriptional regulation of IFNtau genes had been examined using human choriocarcinoma cell lines, JEG-3 or JAR, however, molecular mechanisms by which cell and term specific IFNtau expression are regulated have not been elucidated. Recently, a feeder cell free-trophoblast cell line derived from Shiba-goat placenta, termed HTS-1, was established. In the present investigation, the 5'-upstream region of ovine IFNtau (oIFNtau) gene was analysed using this cell line, which would provide a more suitable system for studies of the ovine trophoblast specific gene than human choriocarcinoma cells. Variously modified 5'-upstream sequences of the oIFNtau gene fused to a luciferase reporter gene were transiently transfected into HTS-1 cells, and human JEG-3 cells were used as a control. These results and co-transfection with expression vectors revealed that Ets-2 binding site in the promoter region was important in HTS-1, whereas AP-1 that binds to the enhancer region was a major activator in JEG-3. By electrophoretic mobility shift assay, a nuclear protein from HTS-1 cells was confirmed to bind specifically to the Ets-2 site of oIFNtau promoter region. Differences in amounts of AP-1 and Ets-2 protein were demonstrated in nuclear extracts from HTS-1, JEG-3 and ovine conceptuses. Substantial differences on oIFNtau gene transcriptions found between caprine HTS-1 and human JEG-3 cells suggest that this cell line could be valuable in the elucidation of a molecular mechanism(s) by which oIFNtau gene expression is regulated in a cell specific manner.

'Steady/equilibrium approximation' in relaxation and fluctuation. II. Mathematical theory of approximations in first-order reaction.

A mathematical theory of the steady/equilibrium approximation for first-order reactions is presented. This gives the theoretical basis for the methods of simplifying the complex first-order reactions described in the preceding work The steady/equilibrium relation holds on every fast component after a proper inducation period T degrees T degrees is either of O(1) or less, or nearly of O(1/epsilon) depending on the reaction scheme and on the initial condition but is always less than O(1/epsilon) (as in the preceding paper [1], we use the symbol O(1) to denote a positive number of the order of unity). In the open group, the determinant of the submatrix M(p), representing the interconversion between the fast components in the group and their dissipation, is of O(1). The concentration of the fast components in the open group can thus be expressed as a linear combination of those components neighboring the group after the establishment of a steady/equilibrium relation, and can be eliminated from the reaction scheme leaving the pathway through them. On the other hand, in the closed group the determinant of Mp is of O(epsilon) or less and the components in the group are in quasi equilibrium with each other after T degrees . They are eliminated from the reaction scheme leaving the sum of the components in the closed group as a slow component.

'Steady/equilibrium approximation' in relaxation and fluctuation. I. Procedure to simplify first-order reaction.

A general procedure to simplify a complex first-order reaction by two approximations, the principle of fast equilibration and the steady-state approximation, is presented. Rate constants are classified into two groups: those of the order of unity and those of the order of epsilon (much less than 1) or less, and are represented in the schemes by thick and thin arrows, respectively. The fast and the slow components are defined: from the fast component at least one thick arrow originates and from the slow component no thick arrow originates. Fast components are divided into several groups. In a group, the fast components are connected by thick arrows in both directions in each reaction step. When at least one thick arrow originates from the components in a group G and terminates on a component not belonging to group G (group G is open), then the steady-state approximation or principle of fast equilibration holds on each component in group G after an induction period To. When no thick arrow originating from group G is directed to components not belonging to group G (group G is closed), the principle of fast equilibration holds on the fast components in group G after To. The induction period To is less than the order of 1/epsilon.

[The biological activity of vitamin E].

The relative biopotency of alpha-(RRR(d)-, 2-ambo (dl)-and all-rac (dl)), beta-, gamma- and delta-tocopherol, tocotrienol homologues and tocopherol derivatives are summarized in the tables. The new United States Pharmacopoeia [USP] XXII-NFXVII (1990) does not mention the USP (International) Unit of the six different forms of alpha-tocopherol that has indicated the difference in biopotency between d-alpha-tocopherol and dl-(2- ambo)-alpha-tocopherol and been used for 40 years from 1950. Metabolic and bio-discrimination studies of tocopherols are necessary to determine the precise relative biopotency of d-(RRR)-and dl-(all-rac)-alpha tocopherol. The synergistic effect of all-rac-alpha- tocopherol with its 8 stereoisomers and the biotransformation from beta-, gamma-and delta-to alpha-tocopherol are also subjects for further study of the biological activity of tocopherols.

Time-course curves of enzyme reactions with dilute substrates can be determined from the reverse reactions.

We present a novel and useful principle that can be applied to enzyme reactions with dilute substrates and enables to obtain the desired time-course curve from the reverse reaction when the latter can be measured more easily. Let us imagine an enzyme mixture that can catalyze the interconversion between substances A, B, C,.... If one substance (sufficiently dilute) is added to the mixture as the substrate and the time-course curve of the concentration of another substance is followed, then, "the time-course curve of A-->B" (which is the time-course curve of the concentration of substance B when substance A is added as the substrate) and that of the reverse reaction B-->A will coincide when plotted at appropriate scales of magnitude. Similar relation holds on any pair of substances even if they are widely separated in any type of reaction scheme. The principle was proved mathematically and holds on any first-order reaction network and can be applied on an enzyme reaction with a dilute substrate because it is reduced to a first-order reaction network. An example of experimental application of this principle is also given.