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1.
Opt Express ; 32(7): 12520-12527, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571072

ABSTRACT

We demonstrate high-output-power and high-efficiency operation of 1.3-µm-wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). By introducing a metal reflector and adjusting the phase of the reflected light via optimization of the thickness of the p-InP cladding layer, we successfully achieve an output power of approximately 400 mW with the slope efficiency of 0.4 W/A and the wall-plug efficiency of 20% under CW conditions. In addition, this PCSEL exhibits a narrow circular beam with a divergence angle below 1.6° even at high output powers under CW conditions at temperatures from 15°C to 50°C. We have also demonstrated an output power of over 12 W under pulsed conditions at room temperature.

2.
Entropy (Basel) ; 25(10)2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37895587

ABSTRACT

We introduce the problem of variable-length (VL) source resolvability, in which a given target probability distribution is approximated by encoding a VL uniform random number, and the asymptotically minimum average length rate of the uniform random number, called the VL resolvability, is investigated. We first analyze the VL resolvability with the variational distance as an approximation measure. Next, we investigate the case under the divergence as an approximation measure. When the asymptotically exact approximation is required, it is shown that the resolvability under two kinds of approximation measures coincides. We then extend the analysis to the case of channel resolvability, where the target distribution is the output distribution via a general channel due to a fixed general source as an input. The obtained characterization of channel resolvability is fully general in the sense that, when the channel is just an identity mapping, it reduces to general formulas for source resolvability. We also analyze the second-order VL resolvability.

3.
Opt Express ; 31(16): 26842-26853, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710534

ABSTRACT

Ultracompact mode multiplexers based on mosaic structure for various wavelength bands designed by Bayesian technique are investigated. C-, O-, and C + O band, TE0-TE1 2-mode multiplexers can be designed with the same footprint, by only changing the mosaic-pattern, showing the great flexibility of mosaic-based devices. Bayesian direct binary search method is used for the design, and it is demonstrated that the Bayesian technique is superior to conventional design method in terms of the best-structure search for the same number of iterations. The designed devices are fabricated for Si-waveguide platform, and the proof-of-concept results are obtained. These results indicate that the mosaic-based devices are promising candidates for future compact optical transceivers.

4.
Entropy (Basel) ; 25(6)2023 Jun 11.
Article in English | MEDLINE | ID: mdl-37372265

ABSTRACT

The utilization of databases such as IoT has progressed, and understanding how to protect the privacy of data is an important issue. As pioneering work, in 1983, Yamamoto assumed the source (database), which consists of public information and private information, and found theoretical limits (first-order rate analysis) among the coding rate, utility and privacy for the decoder in two special cases. In this paper, we consider a more general case based on the work by Shinohara and Yagi in 2022. Introducing a measure of privacy for the encoder, we investigate the following two problems: The first problem is the first-order rate analysis among the coding rate, utility, privacy for the decoder, and privacy for the encoder, in which utility is measured by the expected distortion or the excess-distortion probability. The second task is establishing the strong converse theorem for utility-privacy trade-offs, in which utility is measured by the excess-distortion probability. These results may lead to a more refined analysis such as the second-order rate analysis.

5.
Int J Neural Syst ; 33(2): 2350004, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36624957

ABSTRACT

Error-correcting output coding (ECOC) is a method for constructing a multi-valued classifier using a combination of given binary classifiers. ECOC can estimate the correct category by other binary classifiers even if the output of some binary classifiers is incorrect based on the framework of the coding theory. The code word table representing the combination of these binary classifiers is important in ECOC. ECOC is known to perform well experimentally on real data. However, the complexity of the classification problem makes it difficult to analyze the classification performance in detail. For this reason, theoretical analysis of ECOC has not been conducted. In this study, if a binary classifier outputs the estimated posterior probability with errors, then this binary classifier is said to be noisy. In contrast, if a binary classifier outputs the true posterior probability, then this binary classifier is said to be noiseless. For a theoretical analysis of ECOC, we discuss the optimality for the code word table with noiseless binary classifiers and the error rate for one with noisy binary classifiers. This evaluation result shows that the Hamming distance of the code word table is an important indicator.

6.
Opt Express ; 30(16): 29539-29545, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36299127

ABSTRACT

We demonstrate high-power continuous-wave (CW) lasing oscillation of 1.3-µm wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). Single-mode operation with an output power of over 100 mW, a side-mode suppression ratio (SMSR) of over 50 dB, and a narrow single-lobe beam with a divergence angle of below 1.2° are successfully achieved by using a double-lattice photonic crystal structure consisting of high-aspect-ratio deep air holes. The double lattice is designed to enhance both the in-plane optical feedback and the surface radiation effects in the photonic crystal. The coupling coefficients for 180 ∘, +90 ∘, and -90 ∘ diffractions are estimated from the measurements of the photonic band structure as κ1D = 417 cm-1, κ2D+ = 135 cm-1, and κ2D- = 65 cm-1, respectively. The stable single-mode, high-beam-quality operation is attributed to these large coupling coefficients introduced by the asymmetric double-lattice structure.

7.
Biomed Pharmacother ; 153: 113363, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35834989

ABSTRACT

OBJECTIVE: The improvements of antitumor effects and tolerability on chemotherapy for advanced hepatocellular carcinoma (HCC) are warranted. Here, we aimed to elucidate the mechanism of the combining effect of tyrosine kinase inhibitor sorafenib (SOR) and iron chelator deferasirox (DFX) in human hepatoma cell lines, HepG2 and Huh-7. METHODS: The types of programmed cell deaths (PCDs); necrosis/necroptosis and apoptosis, were evaluated by flow cytometry and fluorescent microscopy. Human cleaved caspase-3 was analyzed by ELISA for apoptosis. GSH assay was used for ferroptosis. PCDs inhibition was analyzed by adding apoptosis inhibitor Z-VAD-FMK, ferroptosis inhibitor ferrostatin-1, necroptosis inhibitor necrosulfonamide, respectively. The expression of NF-κB was quantified by Western blotting. RESULTS: In SOR monotherapy, cleaved caspase-3 expression was increased in all concentrations, confirming the result that SOR induces apoptosis. In SOR monotherapy, GSH/GSSG ratio was decreased on concentration-dependent, showing that SOR also induced ferroptosis. Lipid Peroxidation caused by SOR, corresponding to ferroptosis, was suppressed by DFX. In fluorescence microscopy of SOR monotherapy, apoptosis was observed at a constant rate on all concentrations, while necroptosis and ferroptosis were increased on high concentration. In sorafenib and deferasirox combinations, sub G1 phase increased additively. In SOR and DFX combinations, the cytotoxic effects were not suppressed by ferrostatin-1, but suppressed by Z-VAD-FMK and necrosulfonamide. In each monotherapy, and SOR + DFX combinations, the expression of NF-κB in nucleus was suppressed. Regarding PCD by SOR and DFX combination, ferroptosis was suppressed and both apoptosis and necroptosis became dominant. CONCLUSION: Suppression of NF-κB is possibly involved in the effect of DFX. As a result, SOR and DFX combination showed additive antitumor effects for HCC through the mechanism of programed cell deaths and NF-kB signal modification.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Apoptosis , Carcinoma, Hepatocellular/pathology , Caspase 3 , Cell Line , Cell Line, Tumor , Deferasirox/pharmacology , Deferasirox/therapeutic use , Humans , Iron Chelating Agents/pharmacology , Iron Chelating Agents/therapeutic use , Liver Neoplasms/pathology , NF-kappa B/pharmacology , Sorafenib/pharmacology , Sorafenib/therapeutic use
8.
Entropy (Basel) ; 24(5)2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35626520

ABSTRACT

We consider a binary classification problem for a test sequence to determine from which source the sequence is generated. The system classifies the test sequence based on empirically observed (training) sequences obtained from unknown sources P1 and P2. We analyze the asymptotic fundamental limits of statistical classification for sources with multiple subclasses. We investigate the first- and second-order maximum error exponents under the constraint that the type-I error probability for all pairs of distributions decays exponentially fast and the type-II error probability is upper bounded by a small constant. In this paper, we first give a classifier which achieves the asymptotically maximum error exponent in the class of deterministic classifiers for sources with multiple subclasses, and then provide a characterization of the first-order error exponent. We next provide a characterization of the second-order error exponent in the case where only P2 has multiple subclasses but P1 does not. We generalize our results to classification in the case that P1 and P2 are a stationary and memoryless source and a mixed memoryless source with general mixture, respectively.

9.
Nagoya J Med Sci ; 84(1): 155-162, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35392003

ABSTRACT

The purpose of this study is to examine trends in spine surgeries at ten facilities over 15 years, and to analyze relationships with the number of spine surgeons at these facilities. The subjects were patients who underwent spine surgery at the ten facilities from 2003 to 2017. Data were collected every year via a questionnaire designed to obtain clinicopathological and surgical information. There were 37,601 spine surgeries (60.2% male) recorded in the registry at 9 facilities in the Nagoya Spine Group (NSG) between 2003 and 2017, with an increase in the annual number of surgeries by 2.4 times over 15 years. On the other hand, the number of spine surgeons has increased by just under 1.5 times. Instrumentation surgeries increased from 959 in 2003 to 2,276 in 2017 (2.3 times). There was a particularly marked increase in surgeries for spinal degenerative disease from 1,075 in 2003 to 2,821 in 2017 (2.6 times). The number of surgeries performed per surgeon increased from 61.4 in 2003 to 102.8 in 2017, while the average number of spine surgeons per hospital increased from 2.6 in 2003 to 3.7 in 2017. In conclusion, with heavier burden on spine surgeons and the major changes in the spine surgery environment, training and increasing surgeons with advanced expertise and skills will become increasingly important.


Subject(s)
Spine , Surgeons , Female , Humans , Male , Spine/surgery , Surveys and Questionnaires
10.
Entropy (Basel) ; 23(8)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34441189

ABSTRACT

In the present paper, we investigate the fundamental trade-off of identification, secret-key, storage, and privacy-leakage rates in biometric identification systems for remote or hidden Gaussian sources. We use a technique of converting the system to one where the data flow is in one-way direction to derive the capacity region of these rates. Also, we provide numerical calculations of three different examples for the system. The numerical results imply that it seems hard to achieve both high secret-key and small privacy-leakage rates simultaneously.

11.
Opt Lett ; 46(10): 2312-2315, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33988571

ABSTRACT

A Kerr-lens mode-locked (KLM) thin-disk laser with Yb:LuAG ceramic was demonstrated. Yb:LuAG ceramic is an attractive material for high-power lasers due to its high thermal conductivity and large emission cross section. The highest output power of 17 W with a pulse duration of 130 fs was achieved. Moreover, the pulse duration of 88 fs was also obtained with a high-Q factor cavity. To the best of our knowledge, this is the first demonstration of a KLM thin-disk laser based on Yb:LuAG, including both ceramic and single crystal. The results show the usefulness of ceramic thin disks for high-power ultrashort pulse laser sources.

12.
Anat Rec (Hoboken) ; 304(5): 1136-1150, 2021 05.
Article in English | MEDLINE | ID: mdl-33034098

ABSTRACT

Histidine decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage-committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2-, 3-, and 6-week-old wild-type mice. We also performed morphological analyses of the hematopoietic sites using HDC-deficient (HDC-KO) mice. In wild-type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age-dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC-KO mice compared to wild-type mice. In the liver, HDC expression was temporarily increased at 3 weeks and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC-KO mice compared to wild-type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220-positive B-lymphocytes and TER119-positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC-KO mice upon N-acetyl histamine treatment. A significant increase in the expression of hematopoiesis-related cytokines, Il3, Il7, Epo, Gcsf, and Cxcl12 mRNA was observed in the liver of 3-week-old HDC-KO mice compared to wild-type mice. These results suggest that histamine-deficiency may maintain an microenvironment suitable for hematopoiesis by regulating hematopoiesis-related cytokine expression in the liver of postnatal mice.


Subject(s)
Hematopoiesis, Extramedullary/physiology , Histidine Decarboxylase/metabolism , Liver/metabolism , Spleen/metabolism , Animals , Histidine Decarboxylase/genetics , Mice , Mice, Knockout
13.
J Orthop Sci ; 26(4): 555-559, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32800525

ABSTRACT

BACKGROUND: Postoperative SSI is a common and potentially serious complication in spine surgery. Seasonal variation occurs in rates of nosocomial infection, with higher rates found in the summer, during which hot, humid conditions may be optimal for proliferation of bacteria. This might also influence the rate of SSI. The purpose of the study was to examine seasonal variation in SSI after PLIF/TLIF surgery, including relationships with experience of surgeons and causal organisms. METHODS: Cases with SSI after PLIF/TLIF surgery at 10 facilities between January 1, 2012, and December 31, 2014 were retrieved from a database. Infection was defined based on CDC guidelines for SSIs. Patients were followed for at least two years after surgery. Surgeries were examined in spring (April-June), summer (July-September), autumn (October-December), and winter (January-March). Seasonal variation and other factors with a potential association with SSIs were evaluated. RESULTS: A total of 1174 patients (607 males, 567 females) who underwent PLIF/TLIF surgery were identified. The operations were PLIF (n = 667), TLIF (n = 443), MIS-PLIF (n = 27), and MIS-TLIF (n = 37). The total SSI rate for the 2-year period was 2.5% (29/1174), and the 2-year average SSI rates for surgeries in each season were spring, 2.6% (7/266); summer, 3.9% (13/335); fall, 1.3% (4/302); winter, 1.8% (5/271). The SSI rate was significantly higher in summer than non-summer (3.9% vs. 1.9%, p < 0.05). SSIs were caused by a variety of pathogens, including Gram-positive cocci, and Staphylococcus aureus was the most common pathogenic organism to cause SSI. CONCLUSION: Seasonality should be taken into account in strategies for SSI prevention, with particular attention on mitigation of increased temperature and humidity in the summer and on infection caused by Gram-positive cocci and S. aureus.


Subject(s)
Lumbar Vertebrae , Spinal Fusion , Female , Humans , Incidence , Male , Minimally Invasive Surgical Procedures , Seasons , Surgical Wound Infection/epidemiology
14.
Opt Express ; 28(24): 35483-35489, 2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33379661

ABSTRACT

We report on electrically driven InP-based photonic-crystal surface-emitting lasers (PCSELs), which possess a deep-air-hole photonic crystal (PC) structure underneath an active region formed by metal-organic vapor-phase-epitaxial (MOVPE) regrowth. Single-mode continuous-wave (CW) lasing operation in 1.3-µm wavelength is successfully achieved at a temperature of 15°C. It is shown that the enhancement of lateral growth during the MOVPE regrowth process of air holes enables the formation of deep air holes with an atomically flat and thin overlayer, whose thickness is less than 100 nm. A threshold current of 120 mA (threshold current density = 0.68 kA/cm2) is obtained in a device with a diameter of 150 µm. A doughnut-like far-field pattern with the narrow beam divergence of less than 1° is observed. Strong optical confinement in the PC structure is revealed from measurements of the photonic band structure, and this strong optical confinement leads to the single-mode CW lasing operation with a low threshold current density.

15.
Opt Express ; 28(13): 19772-19782, 2020 Jun 22.
Article in English | MEDLINE | ID: mdl-32672247

ABSTRACT

We demonstrate low-loss and broadband light transition from III-V functional layers to a Si platform via two-stage adiabatic-crossing coupler waveguides. A 900-µm-long and 2.7-µm-thick III-V film waveguide consisting of a GaInAsP core and InP cladding layers is transferred onto an air-cladding Si photonic chip by the µ-transfer printing (µ-TP) method. An average optical coupling loss per joint of 1.26 dB is obtained in C + L telecommunication bands (1530-1635 nm). The correlation between alignment offset and measured optical coupling loss is discussed with the frequency distribution of µ-TP samples. We also performed a photoluminescence measurement to investigate the material properties in the GaInAsP layer to see if they are distorted by the strong bending stress produced during the pick-up and print steps of the µ-TP process. The peak intensity reduction of 80-90% and a wavelength shift of 0-5 nm (blue shift) were observed after the process. The series of fundamental studies presented here, which combine multiple analyses, contribute to improving our understanding of III-V/Si photonic integration by µ-TP.

16.
J Nat Prod ; 82(10): 2754-2760, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31596079

ABSTRACT

Six new prenylated acylphloroglucinols with menthane moieties, hypascyrins A-E (1-5) and ent-hyphenrone J (6), together with four known analogues, were isolated from Hypericum ascyron roots. Detailed spectroscopic data analyses resulted in the assignment of their structures. The absolute configuration of 1 was deduced by experimental and calculated ECD data, while those of 2-6 were assigned by ECD data analyses as well as chemical conversions. Hypascyrins A (1), C (3), and E (5) and ent-hyphenrone J (6) exhibited antimicrobial activity against MRSA (MIC50 values of 4.0, 8.0, 2.0, and 4.0 µM, respectively) and Bacillus subtilis (MIC values of 4.0, 4.0, 2.0, and 4.0 µM, respectively).


Subject(s)
Anti-Infective Agents/isolation & purification , Hypericum/chemistry , Phenols/isolation & purification , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacillus subtilis/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Phenols/chemistry , Phenols/pharmacology , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Plant Roots/chemistry , Prenylation
17.
Global Spine J ; 9(5): 466-472, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31431867

ABSTRACT

STUDY DESIGN: Retrospective analysis of a prospectively database. OBJECTIVES: To identify factors associated with prolonged length of stay (LOS) in posterior /transforaminal lumbar interbody fusion (PLIF/TLIF). METHODS: The subjects were patients who underwent PLIF/TLIF at 10 facilities from 2012 to 2014. A total of 1168 such patients with a mean age of 65.9 ± 12.5 years (range 18-87 years) were identified in the database. Operations were PLIF (n = 675), TLIF (n = 443), minimally invasive surgery (MIS)-PLIF (n = 22), and MIS-TLIF (n = 32). Age, gender, body mass index, ambulatory status, comorbidities, perioperative American Society of Anesthesiologists (ASA) grade, operative factors, and complications were examined. LOS was defined as the number of calendar days from the operation to hospital discharge. LOS was categorized as normal (<75th percentile) or prolonged (≥75th percentile). RESULTS: The average LOS was 20.8 ± 9.8 days (range 7-77 days). There was a significant correlation between LOS and age (P < .05). Reoperation during hospitalization was performed in 20 cases for surgical site infection (n = 12), epidural hematoma (n = 5), and screw misplacement (n = 3). In multivariate analysis, prolonged LOS was associated with preoperative variables of age ≥70 years (odds ratio [OR] 1.87, 95% CI 1.38-2.54), and ASA class ≥III (OR 1.52, 95% CI 1.04-2.25); surgical variables of open procedures (OR 5.84, 95% CI 1.74-19.63), fused levels ≥3 (OR 5.17, 95% CI 3.17-8.43), operative time ≥300 minutes (OR 1.88, 95% CI 1.15-3.07), and estimated blood loss ≥500 mL (OR 1.71, 95% 1.07-2.75). CONCLUSIONS: The factors identified in this study should help with obtaining informed consent, surgical planning and complication prevention to reduce health care costs associated with prolonged LOS.

18.
Biol Pharm Bull ; 42(6): 929-936, 2019.
Article in English | MEDLINE | ID: mdl-31155589

ABSTRACT

Bisphosphonates (BPs) containing nitrogen (N-BPs) exhibit far stronger anti-bone-resorptive effects than non-N-BPs. However, repeated administration of N-BPs causes osteonecrosis selectively in jawbones. As BPs accumulate in large amounts within inflamed bones, any N-BP released from the pool accumulated within jawbones might directly act on cells in the surrounding soft-tissues and induce inflammation or necrosis. Here, we examined the local and systemic effects of zoledronate (the most potent N-BP with the highest incidence of jawbone-necrosis) on inflammatory cytokines in mice. Locally within ear-pinnas: (i) zoledronate induced long-lasting accumulation of interleuikin-1ß (IL-1ß) and IL-18, but not tumor necrosis factor-α (TNF-α), (ii) zoledronate and lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria) mutually augmented the productions of IL-1ß, IL-18, and TNF-α, and (iii) oxidronate (a toxic non-N-BP) by itself produced not only IL-1ß and IL-18, but also TNF-α. In systemic experiments using intraperitoneal injection of zoledronate and/or LPS, (i) zoledronate by itself increased none of the above cytokines in serum, and (ii) in mice pretreated (3 d before) with zoledronate, the LPS-induced increases in serum IL-1ß and IL-18 were greatly augmented with a delayed slight TNF-α augmentation. These results, together with previous ones, suggest that (a) pro-IL-1ß and pro-IL-18 accumulate within cells in soft-tissues exposed to N-BPs, and infection may augment not only their production, but also the release of their mature forms, (b) IL-1ß and IL-18 (possibly together with TNF-α) may play important roles in N-BP-induced inflammation and/or necrosis, and (c) mechanisms underlying the cytotoxic effects of BPs may differ between N-BPs and non-N-BPs.


Subject(s)
Bone Density Conservation Agents/pharmacology , Ear Auricle/drug effects , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Zoledronic Acid/pharmacology , Animals , Ear Auricle/metabolism , Lipopolysaccharides/pharmacology , Mice, Inbred BALB C
19.
Clin Neurol Neurosurg ; 177: 97-100, 2019 02.
Article in English | MEDLINE | ID: mdl-30640049

ABSTRACT

OBJECTIVES: To identify factors associated with prolonged length of stay (LOS) in spine surgery, with the goal of establishing details of LOS for multiple diseases and surgical procedures. PATIENTS AND METHODS: The subjects were patients who underwent spine surgery at 10 facilities in the Nagoya Spine Group from January 2005 to December 2015. Data were collected for patient background, primary spinal pathology, anatomical location of the lesion, and surgical methods. The primary outcome was LOS, which was defined as the calendar days from surgery to hospital discharge. RESULTS: A total of 10,829 patients (5953 males, 4876 females; age 5-93 years, mean 60.2 ± 28.8 years) were identified in the database. Average follow-up was 61 months (range: 13-120 months). Average LOS was 22.3 ± 21.3 days, and there was a gradual decrease in LOS over the study period. LOS was significantly correlated with age, and prolonged LOS was significantly associated with thoracic spine surgery and significantly longer after surgery with instrumentation. Average LOS was >30 days for intramedullary tumor resection and posterior cervical fusion, but only 10.2 days for microendoscopic discectomy. Reoperation was performed in 210 patients (1.9%) and these patients had a significantly higher average LOS of 43.1 days. CONCLUSION: These results will assist quality improvement in spine surgery. The identified risk factors for prolonged LOS will also assist in planning of surgery, postoperative care, and discharge, with the goal of reducing health care costs.


Subject(s)
Length of Stay/statistics & numerical data , Patient Discharge/statistics & numerical data , Postoperative Complications/surgery , Spinal Diseases/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Databases, Factual , Elective Surgical Procedures , Female , Humans , Japan , Male , Middle Aged , Patient Readmission/statistics & numerical data , Postoperative Period , Reoperation/methods , Risk Factors , Spinal Fusion/methods , Young Adult
20.
Cancer Sci ; 110(2): 674-685, 2019 02.
Article in English | MEDLINE | ID: mdl-30548114

ABSTRACT

L-Type amino acid transporter 1 (LAT1) disulfide linked to CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti-LAT1 mAbs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody-dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side-effects of antihuman LAT1 mAbs in clinical trials. Antihuman LAT1 mAbs reacted with ACHN human and MK.P3 macaca kidney-derived cells, and this reactivity was significantly decreased by siRNAs against LAT1. Macaca LAT1 cDNA was cloned from MK.P3, and only two amino acid differences between human and macaca LAT1 were seen. RH7777 rat hepatoma and HEK293 human embryonic kidney cells expressing macaca LAT1 were established as stable transfectants, and antihuman LAT1 mAbs were equivalently reactive against transfectants expressing human or macaca LAT1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT1, MK.P3, ACHN and HCT116 human colon cancer cells, and KA values were increased by anti-CD98hc mAb, suggesting anti-LAT1 mAbs detect an epitope on LAT1-CD98hc complexes on the cell surface. Based on these results, LAT1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mAbs.


Subject(s)
Antibodies, Monoclonal/pharmacology , Large Neutral Amino Acid-Transporter 1/metabolism , A549 Cells , Amino Acids/metabolism , Animals , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , HCT116 Cells , HEK293 Cells , Haplorhini , HeLa Cells , Humans , Macaca fascicularis , Mice , Mice, Nude , Rats , Rats, Inbred F344
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