[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].

The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.

A Novel Acetyl-CoA Carboxylase 2 Selective Inhibitor Improves Whole-Body Insulin Resistance and Hyperglycemia in Diabetic Mice through Target-Dependent Pathways.

Excess intramyocellular lipid (IMCL) deposition in skeletal muscle is closely associated with insulin resistance. Pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 offers a promising approach to treat insulin resistance through stimulation of mitochondrial fatty acid oxidation (FAO) and reduction of IMCL deposition. Previously reported experimental ACC2 inhibitors exhibited plasma glucose-lowering effects in diabetic rodents. However, their antidiabetic action may be potentially biased by off-target effects on triglyceride metabolism or by neurologic side effects. In this study, we investigated a safety profile, target dependency of its action, and antidiabetic efficacy of compound 2e, a novel olefin derivative potent ACC2 selective inhibitor. Four-day administration of suprapharmacological dose of compound 2e did not exhibit any obvious side effects in Sprague-Dawley rats. In db/db mice, single administration of compound 2e led to significantly elevated FAO and reduced IMCL deposition in skeletal muscle. In ACC2 knockout mice, treatment with pharmacological doses of compound 2e did not reduce plasma triglyceride levels, whereas A-908292, a previously reported ACC2 inhibitor, caused a significant triglyceride reduction, showing that compound 2e was devoid of off-target triglyceride-lowering activity. Chronic treatment of db/db mice with compound 2e improved hyperglycemia but did not decrease plasma triglyceride levels. Additionally, compound 2e showed significant improvements of whole-body insulin resistance in the clamp study and insulin tolerance test. Collectively, compound 2e demonstrated a good safety profile and significant antidiabetic effects through inhibition of ACC2-dependent pathways. These findings provide further evidence that selective inhibition of ACC2 is an attractive strategy against insulin resistance and type 2 diabetes. SIGNIFICANCE STATEMENT: This study shows that pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 leads to significant improvements in whole-body glucose homeostasis, independently of off-target metabolic pathways and toxicity, which were observed in previously reported ACC2 inhibitors. These findings support the concept that ACC2-selective inhibitors will be a novel remedy for treatment of type 2 diabetes.

Error-free reconstruction of magnetic hologram via improvement of recording conditions in collinear optical system.

Magnetic holographic memory is expected as a rewritable high-capacity data storage technology. To improve the reconstructed image, we investigate recording conditions by numerical simulation and experiments. We found experimentally that four diffracted beams from a digital micromirror device interfere with each other at a suitable defocus recording point, and such overlapping is favorable to obtain clear reconstruction images without diffuser. Subsequently, we modify the shape of the reference beam to ensure more effective interference. As a result, we achieve error-free image reconstruction from the magnetic hologram. Our results indicate that magnetic holograms can potentially be utilized as holographic memory.

Thermomagnetic writing into magnetophotonic microcavities controlling thermal diffusion for volumetric magnetic holography.

Holographic memory is expected to become a high-capacity data storage. Magnetic volumetric holograms are rewritable holograms that are recorded as magnetization directions through thermomagnetic recording. However, the effective depth of magnetic holograms is limited by thermal diffusion that causes merging of magnetic fringes. In this study, we propose the insertion of heat-sink layers (HSLs) for retaining well-defined magnetic fringes during volumetric writing. Magnetophotonic microcavity media were used for demonstrating the HSL effect, and the structural design principle was established in numerical calculations. The results indicate that deep and clear magnetic fringes and an improvement in the diffraction efficiency can be achieved by the insertion of HSLs.

Magnetophotonic crystal with cerium substituted yttrium iron garnet and enhanced Faraday rotation angle.

Magnetophotonic crystals (MPCs) comprising cerium-substituted yttrium iron garnet (CeYIG) sandwiched by two Bragg mirrors were fabricated by vacuum annealing. CeYIG was deposited on Bragg mirrors at room temperature and annealed in 5 Pa of residual air. No ceria or other non-garnet phases were detected. Cerium 3 + ions substituted on the yttrium sites and no cerium 4 + ions were found. The Faraday rotation angle of the MPC was -2.92° at a wavelength of λ = 1570 nm was 30 times larger than that of the CeYIG film. These results showed good agreement with calculated values derived using a matrix approach.

Magneto-optical Q-switching using magnetic garnet film with micromagnetic domains.

High-power giant pulses can be used applied in various applications with Q-switched micro-lasers. This method can shorten the pulse duration; however, active control is currently impossible in micro-lasers. To achieve precise pulse control while maintaining compactness and simplicity, we exploit the magneto-optical effect in magnetic garnet films with micromagnetic domains that can be actively controlled by a pulsed magnetic field. Our Q-switching technique enhances the output power by a factor of 4 × 103. Moreover, the device itself is smaller than other Q-switching devices. This novel type of active Q-switch can be combined with a micro-laser to obtain megawatt-order pulses.

Direct Observation of Two-Step Photon Absorption in an InAs/GaAs Single Quantum Dot for the Operation of Intermediate-Band Solar Cells.

We present the first direct observation of two-step photon absorption in an InAs/GaAs single quantum dot (QD) using photocurrent spectroscopy with two lasers. The sharp peaks of the photocurrent are shifted due to the quantum confined Stark effect, indicating that the photocurrent from a single QD is obtained. In addition, the intensity of the peaks depends on the power of the secondary laser. These results reveal the direct demonstration of the two-step photon absorption in a single QD. This is an essential result for both the fundamental operation and the realization of ultrahigh solar-electricity energy conversion in quantum dot intermediate-band solar cells.

Collinear volumetric magnetic holography with magnetophotonic microcavities.

Hologram memory is a candidate for high-capacity data storage. Magnetic holograms formed as magnetization directions have been studied to realize rewritable hologram media. Recently, we reported that the magnetophotonic microcavity (MPM) can improve diffraction efficiency because of enhanced Faraday rotation angle and deep hologram writing. In this study, we demonstrated a clear reconstructed image from magnetic holograms in an MPM medium. The structural condition of MPMs for high diffraction efficiency was investigated, and the MPM medium was actually fabricated. The image reconstructed from the MPM medium had approximately twice the brightness of that reconstructed using a monolayer film.

Development of an ultrasensitive immunoassay using affinity maturated antibodies for the measurement of rodent insulin.

The measurement of plasma insulin is important for clinical diagnosis of diabetes and for preclinical research of metabolic diseases, especially in rodent models used in drug discovery research for type 2 diabetes. Fasting immunoreactive insulin (F-IRI) concentrations are used to calculate the homeostasis model assessment ratio (HOMA-R), an index of insulin sensitivity. However, even the most sensitive commercially available enzyme-linked immunosorbent assay (ELISA) kits cannot measure the very low F-IRI concentrations in normal rats and mice. Therefore, we sought to develop a new rodent insulin ELISA with greater sensitivity for low F-IRI concentrations. Despite repeated efforts, high-affinity antibodies could not be generated by immunizing mice with mouse insulin (self-antigen). Therefore, we generated two weak monoclonal antibodies (13G4 and 26B2) that were affinity maturated and used to develop a highly sensitive ELISA. The measurement range of the sandwich ELISA with the affinity maturated antibodies (13G4m1 and 26B2m1) was 1.5 to 30,000 pg/ml, and its detection limit was at least 10 times lower than those of commercially available kits. In conclusion, we describe the development of a new ultrasensitive ELISA suitable for measuring very low plasma insulin concentrations in rodents. This ELISA might be very useful in drug discovery research in diabetes.

Rare cause of severe anemia due to pyogenic granuloma in the jejunum.

BACKGROUND: Pyogenic granuloma (PG) is a polypoid lobular capillary hemangioma rarely observed in the gastrointestinal tract. Only a few cases in the small bowel have been described in the literature. CASE PRESENTATION: A 58-year-old man had been suffering from general fatigue and severe anemia. Esophagogastroduodenoscopy and colonoscopy did not reveal any significant bleeding. Abdominal computer tomography revealed a hypervascular tumor in the small intestine. Oral double-balloon endoscopy (DBE) detected a polypoid lesion (2 cm in diameter) in the jejunum. We performed laparoscopic-assisted partial resection of the jejunum. The histological features of the tumor were consistent with PG. The patient's anemia gradually improved without the need for oral iron after surgery. CONCLUSION: In this case report, we present a case of pyogenic granuloma in in the jejunum that was detected by DBE.

Magnetic volumetric hologram memory with magnetic garnet.

Holographic memory is a promising next-generation optical memory that has a higher recording density and a higher transfer rate than other types of memory. In holographic memory, magnetic garnet films can serve as rewritable holographic memory media by use of magneto-optical effect. We have now demonstrated that a magnetic hologram can be recorded volumetrically in a ferromagnetic garnet film and that the signal image can be reconstructed from it for the first time. In addition, multiplicity of the magnetic hologram was also confirmed; the image could be reconstructed from a spot overlapped by other spots.

Spontaneous rupture of a giant gastrointestinal stromal tumor of the jejunum: a case report and literature review.

A few cases of a gastrointestinal stromal tumor (GIST) of the small intestine presenting as rupture have been reported in the medical literature. We report an unusual case of a large GIST of the jejunum that presented as a spontaneous rupture. A 70-year-old man was referred to our hospital because of fever and abdominal pain. An abdominal enhanced computed tomography (CT) scan detected a 10-cm tumor with heterogeneous staining, suggesting necrosis or abscess inside the tumor. The patient was treated with antibiotics but inflammation persisted and an operation was performed. Intraoperative findings showed an outgrowing 10-cm mass in the jejunum near Treitz's ligament. The tumor had ruptured with peritoneal metastasis. The solid parenchyma contained a focal area of necrosis within and the small ulcer located in the wall of the jejunum presented a communication with the large tumor cavity. H&E staining showed spindle-shaped cell proliferation, and immunohistochemical staining showed results positive for c-kit and CD34. The patient received a diagnosis of a GIST (high-risk group) of the jejunum and was treated with imatinib mesylate. The patient has remained in good health without recurrence or metastasis one year after the surgical procedure.

[A case of primary duodenal cancer recurrence successfully treated with CapeOX therapy].

A 55-year-old man was admitted to our hospital because of nausea and vomiting. An endoscopic examination and computed tomography(CT)scan revealed a duodenal tumor. A biopsy confirmed a diagnosis of primary duodenal adenocarcinoma. A pancreaticoduodenectomy and partial resection of the ascending colon were performed. Ten months after surgery, we observed lymph node recurrence and peritoneal dissemination. We then introduced capecitabine and oxaliplatin (CapeOX)therapy for treatment of the relapsed disease. A partial response(PR)was observed after 2 courses, and was sustained for 5 months. The patient survived another 1 year and 4 months after disease recurrence. CapeOX therapy can be an effective treatment for primary duodenal cancer.

High Q H1 photonic crystal nanocavities with efficient vertical emission.

We report on newly-designed H1-type photonic crystal (PhC) nanocavities that simultaneously exhibit high Q factors, small mode volumes, and high external coupling efficiencies (η([perpendicular])) of light radiated above the PhC membrane. Dipole modes of the H1 PhC nanocavities, which are doubly-degenerate and orthogonally-polarized in theory, are investigated both by numerical calculations and experiments. Through modifying the sizes and positions of the air-holes near to the defect cavity, a Q factor of 62,000 is achieved, accompanied with an improved η([perpendicular]) of 0.38 (assuming an objective lens with a numerical aperture of 0.65). A further increase of η([perpendicular]) to more than 0.60 is observed at the expense of slight degradation of Q factor (down to 50,000). We further experimentally confirm the increase of both Q and η([perpendicular]), using micro-photoluminescence measurements, and demonstrate high Q factors up to 25,000: the highest value ever reported for dipole modes in H1 PhC nanocavities.

Acetyl-CoA carboxylase 2 inhibition reduces skeletal muscle bioactive lipid content and attenuates progression of type 2 diabetes in Zucker diabetic fatty rats.

Intramyocellular lipid (IMCL) accumulation in skeletal muscle is closely associated with development of insulin resistance. In particular, diacylglycerol and ceramide are currently considered as causal bioactive lipids for impaired insulin action. Recently, inhibition of acetyl-CoA carboxylase 2 (ACC2), which negatively modulates mitochondrial fatty acid oxidation, has been shown to reduce total IMCL content and improve whole-body insulin resistance. This study aimed to investigate whether ACC2 inhibition-induced compositional changes in bioactive lipids, especially diacylglycerol and ceramide, within skeletal muscle contribute to the improved insulin resistance. In skeletal muscle of normal rats, treatment of the ACC2 inhibitor compound 2e significantly decreased both diacylglycerol and ceramide levels while having no significant impact on other lipid metabolite levels. In skeletal muscle of Zucker diabetic fatty (ZDF) rats, which exhibited greater lipid accumulation than that of normal rats, compound 2e significantly decreased diacylglycerol and ceramide levels corresponding to reduced long chain acyl-CoA pools. Additionally, in the lipid metabolomics study, ZDF rats treated with compound 2e also showed improved diabetes-related metabolic disturbance, as reflected by delayed hyperinsulinemia as well as upregulated gene expression associated with diabetic conditions in skeletal muscle. These metabolic improvements were strongly correlated with the bioactive lipid reductions. Furthermore, long-term treatment of compound 2e markedly improved whole-body insulin resistance, attenuated hyperglycemia and delayed insulin secretion defect even at severe diabetic conditions. These findings suggest that ACC2 inhibition decreases diacylglycerol and ceramide accumulation within skeletal muscle by enhancing acyl-CoA breakdown, leading to attenuation of lipid-induced insulin resistance and subsequent diabetes progression.

[A case of gastric large cell neuroendocrine carcinoma (LCNEC) for whom chemotherapy of CDDP+CPT-11 proved very effective].

Large cell neuroendocrine carcinoma(LCNEC)is a relatively new category with biological behavior similar to small cell carcinoma. Thus, it is reportedly well treated by the same chemotherapy as for small cell carcinoma. We experienced a case of gastric large cell neuroendocrine carcinoma, treated very effectively by CDDP+CPT-11.60 mg/m(2) of CDDP was administered on day 1, and 60 mg/m(2) of CPT-11 on day 1, 8 and 15. An intermission after administration for 14 days made for one course. Four courses were carried out. A complete response was obtained for a primary gastric lesion and liver metastasis, and a partial response was obtained for lymph node metastases. So far it has showed no change for 6 months after chemotherapy. Both CDDP and CPT-11 are key drugs in the chemotherapy for common gastric cancer, and it is sometimes difficult to distinguish large cell neuroendocrine carcinoma from poorly-differentiated gastric cancer. We found this combination chemotherapy is a suitable regimen for the assumed existence of large cell neuroendocrine carcinoma at the gastric lesion.

Conformational transitions of cyclic D,L-peptides.

Conformational transitions of cyclic D,L-hexapeptides have been studied by first-principles calculations. Geometry optimizations for 20 types of homoresidue cyclic D,L-hexapeptide revealed that the cyclic peptides have two types of energetically stable backbone (extended (E) and bound (B) types); and for each type, the amino acid side chains have two orientations (equatorial and axial). Among the four types of isomer [E-type equatorial (E(eq)), B-type equatorial (B(eq)), E-type axial (E(ax)), and B-type axial (B(ax))], B(ax) is the energetically most preferred by most of the 20 encoded amino acid residues, whereas E(ax) is the least preferred. A search for transition states indicated that six types of conformational transition are possible between the isomers of the cyclic peptide, i.e., the backbone-backbone conversions (E(eq)-B(eq) and E(ax)-B(ax) transitions), the side chain-side chain conversions (E(eq)-E(ax) and B(eq)-B(ax) transitions), and the simultaneous conversions of the backbone and the side-chain orientation (E(eq)-B(ax) and E(ax)-B(eq) transitions). All the six transitions proceed with the breaking of the high molecular symmetry (S(6)) and go through the triangular (C(3)) intermediate structure with either equatorial or axial side-chain orientation.

Coherently driven semiconductor quantum dot at a telecommunication wavelength.

We proposed and demonstrate use of optical driving pulses at a telecommunication wavelength for exciton-based quantum gate operation. The exciton in a self-assembled quantum dot is coherently manipulated at 1.3 microm through Rabi oscillation. The telecom-band exciton-qubit system incorporates standard optical fibers and fiber optic devices. The coherent manipulation of the two-level system compatible with flexible and stable fiber network paves the way toward practical optical implementation of quantum information processing devices.

Chelation of transition metal ions by peptide nanoring.

We have computationally studied the energetics and electronic structures of a chelate system where the guest cation is a transition metal (TM) and the host ligand is a peptide nanoring (PNR). The trapping of a TM cation by a cyclic peptide skeleton is primarily caused by the electrostatic interaction. The exchange interaction plays a secondary role in determining the relative stability in accordance with the spin multiplicity. An interesting feature of this chelate system is that a TM cation can also be trapped by the side-chain aromatic groups of the PNR via pi-d hybridization. However, the spin multiplicity of the system changes the trapped form. When the chelate system has spin singlet multiplicity, a Fe(2+) cation, for example, is not trapped by the single-phenyl group but is preferentially sandwiched by the two phenyl groups. In contrast, a Fe(2+) cation can be trapped by single as well as by double-phenyl groups when the chelate system has higher spin multiplicity, such as triplet and quintet. These two different trapping forms are caused by the difference in the number of valence electrons of TM cations. For this chelate system, the newly occupied molecular orbital (MO) has an interbenzene antibonding character. Therefore, an electron occupying this MO state favors the mutual separation of two benzene molecules. Because the electron occupation of this MO varies in accordance with the spin multiplicity, one can predict the preference for the single-phenyl-group trapping process rather than the double-phenyl-group process systematically as well as consistently.

ACC2 Deletion Enhances IMCL Reduction Along With Acetyl-CoA Metabolism and Improves Insulin Sensitivity in Male Mice.

Intramyocellular lipid (IMCL) accumulation in skeletal muscle greatly contributes to lipid-induced insulin resistance. Because acetyl-coenzyme A (CoA) carboxylase (ACC) 2 negatively modulates mitochondrial fatty acid oxidation (FAO) in skeletal muscle, ACC2 inhibition is expected to reduce IMCL via elevation of FAO and to attenuate insulin resistance. However, the concept of substrate competition suggests that enhanced FAO results in reduced glucose use because of an excessive acetyl-CoA pool in mitochondria. To identify how ACC2-regulated FAO affects IMCL accumulation and glucose metabolism, we generated ACC2 knockout (ACC2-/-) mice and investigated skeletal muscle metabolites associated with fatty acid and glucose metabolism, as well as whole-body glucose metabolism. ACC2-/- mice displayed higher capacity of glucose disposal at the whole-body levels. In skeletal muscle, ACC2-/- mice exhibited enhanced acylcarnitine formation and reduced IMCL levels without alteration in glycolytic intermediate levels. Notably, these changes were accompanied by decreased acetyl-CoA content and enhanced mitochondrial pathways related to acetyl-CoA metabolism, such as the acetylcarnitine production and tricarboxylic acid cycle. Furthermore, ACC2-/- mice exhibited lower levels of IMCL and acetyl-CoA even under HFD conditions and showed protection against HFD-induced insulin resistance. Our findings suggest that ACC2 deletion leads to IMCL reduction without suppressing glucose use via an elevation in acetyl-CoA metabolism even under HFD conditions and offer new mechanistic insight into the therapeutic potential of ACC2 inhibition on insulin resistance.