Publications by authors named "Shinya Inoue"

49 Publications

Coronary Artery Fistula Aneurysm: Pathological Analysis After Surgery.

Cureus 2021 May 8;13(5):e14903. Epub 2021 May 8.

Cardiology, Kawasaki Municipal Ida Hospital, Kawasaki, JPN.

An asymptomatic 75-year-old woman was identified with a 40-mm-sized, round-shaped lesion beside the pulmonary artery on computed tomography (CT). Coronary angiography showed a coronary artery fistula (CAF) with an aneurysm branching from the left anterior descending artery toward the pulmonary artery. The CAF aneurysm (CAFA) was resected and coronary artery bypass graft surgery using the left internal thoracic artery was performed successfully. Pathological analysis revealed that medial depletion similar to segmental arterial mediolysis (SAM) may contribute to aneurysm formation.
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http://dx.doi.org/10.7759/cureus.14903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183465PMC
May 2021

Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide.

Int J Pharm 2021 Jun 24;602:120601. Epub 2021 Apr 24.

Department of Pharmaceutical Health Chemistry, Graduate School of Biomedical Sciences, Tokushima University, Shomachi 1, Tokushima 770-8505, Japan. Electronic address:

Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) for intradermal delivery of nucleic acid therapeutics via weak electricity-mediated intercellular junction cleavage, and subsequent exertion of nucleic acid function. However, the thickened pathological skin in psoriasis hampers permeation of IP-administered macromolecules. Thus, approaches are needed to more strongly cleave intercellular spaces and overcome the psoriatic skin barrier. Herein, we applied a combination of tight junction-opening peptide AT1002 with IP, as synergistic effects of weak electricity-mediated intercellular junction cleavage and the tight junction-opening ability of AT1002 may help overcome thickened psoriatic skin and facilitate macromolecule delivery. Pretreatment with IP of an AT1002 analog exhibiting positively-charged moieties before fluorescence-labeled oligodeoxynucleotide IP resulted in the oligodeoxynucleotide permeation into psoriatic skin, whereas IP of the oligodeoxynucleotide alone did not. Moreover, psoriasis-induced upregulation of inflammatory cytokine mRNA levels was significantly suppressed by NF-κB decoy oligodeoxynucleotide IP combined with the AT1002 analog, resulting in amelioration of epidermis hyperplasia. These results suggest that synergistic effects of IP and an AT1002 analog can overcome thickened psoriatic skin and enable intradermal delivery of NF-κB decoy oligodeoxynucleotide for psoriasis treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120601DOI Listing
June 2021

Buoyancy control in ammonoid cephalopods refined by complex internal shell architecture.

Sci Rep 2021 Apr 13;11(1):8055. Epub 2021 Apr 13.

Division of Paleontology, Frontier Gateway Museum, Glendive, MT, 59330, USA.

The internal architecture of chambered ammonoid conchs profoundly increased in complexity through geologic time, but the adaptive value of these structures is disputed. Specifically, these cephalopods developed fractal-like folds along the edges of their internal divider walls (septa). Traditionally, functional explanations for septal complexity have largely focused on biomechanical stress resistance. However, the impact of these structures on buoyancy manipulation deserves fresh scrutiny. We propose increased septal complexity conveyed comparable shifts in fluid retention capacity within each chamber. We test this interpretation by measuring the liquid retained by septa, and within entire chambers, in several 3D-printed cephalopod shell archetypes, treated with (and without) biomimetic hydrophilic coatings. Results show that surface tension regulates water retention capacity in the chambers, which positively scales with septal complexity and membrane capillarity, and negatively scales with size. A greater capacity for liquid retention in ammonoids may have improved buoyancy regulation, or compensated for mass changes during life. Increased liquid retention in our experiments demonstrate an increase in areas of greater surface tension potential, supporting improved chamber refilling. These findings support interpretations that ammonoids with complex sutures may have had more active buoyancy regulation compared to other groups of ectocochleate cephalopods. Overall, the relationship between septal complexity and liquid retention capacity through surface tension presents a robust yet simple functional explanation for the mechanisms driving this global biotic pattern.
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http://dx.doi.org/10.1038/s41598-021-87379-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044186PMC
April 2021

IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development.

Sci Rep 2021 Mar 4;11(1):5266. Epub 2021 Mar 4.

Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4 T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4 T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4 T cells. Both CD4 T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSFCD4 T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation.
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http://dx.doi.org/10.1038/s41598-021-84624-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933155PMC
March 2021

Extended thoracic endovascular aortic repair for residual aortic dissection after type A aortic dissection repair.

Vascular 2021 Jan 21:1708538120988418. Epub 2021 Jan 21.

Department of Cardiovascular Surgery, Keio University, Tokyo, Japan.

Objective: We investigated the outcomes of extended coverage of the descending thoracic aorta by thoracic endovascular aortic repair (TEVAR) for residual chronic type B aortic dissection after type A aortic dissection (TAAD) repair.

Methods: From November 2015 to August 2020, 36 patients underwent extended TEVAR for residual intimal tear after TAAD repair. We specifically investigated the methods and outcomes of this procedure.

Results: TEVAR consisted of isolated TEVARs ( = 29), single-vessel debranching TEVAR (6), and two-vessel debranching TEVAR (1). The mean time from TAAD repair to TEVAR was 27 ± 33 months (2-86 months). The TEVAR devices used were Valiant (28 cases), GORETAG (4), Relay plus (2), and TX2 (2). Technical success of TEVAR was 100%. The distal ends of the stent grafts were T 8 (1 case), T 9 (5), T 10 (6), T 11 (9), and T 12 (15), with an average of T 11 ± 1. The average length of hospital stay after TEVAR was 9 ± 3 days (5-17 days). There were no surgical/hospital deaths or complications. The average postoperative follow-up period was 21 ± 15 months without death or reintervention.

Conclusions: The short-term outcomes of extended TEVAR for residual chronic type B aortic dissection after TAAD repair were acceptable without perioperative SCI. Aggressive descending thoracic aorta coverage may prevent aortic events, and extended TEVAR may be a preemptive treatment for the downstream aorta. Mid- to long-term results should be clarified.
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http://dx.doi.org/10.1177/1708538120988418DOI Listing
January 2021

Effects of the xanthine oxidase inhibitor, febuxostat, on the expression of monocyte chemoattractant protein-1 and synchronous genes in MDCK cells treated with calcium oxalate monohydrate crystals.

Int J Urol 2021 03 3;28(3):339-345. Epub 2021 Jan 3.

Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

Objectives: To examine the effects of the selective xanthine oxidase inhibitor febuxostat on the expression of inflammation-related genes involved in stone formation.

Methods: Madin-Darby canine kidney cells were exposed to febuxostat, followed by calcium oxalate monohydrate crystals. Monocyte chemoattractant protein-1 messenger ribonucleic acid expression levels were determined by real-time reverse transcription polymerase chain reaction analysis. Deoxyribonucleic acid microarray analysis was utilized to evaluate gene expression.

Results: Calcium oxalate monohydrate crystals activated monocyte chemoattractant protein-1 messenger ribonucleic acid expression in a time- and concentration-dependent manner. Febuxostat suppressed monocyte chemoattractant protein-1 expression. The expression levels of a group of inflammatory genes, including interleukin-8 and chemokine (C-X-C motif) ligand 10, which are downstream of reactive oxygen species, fluctuated similarly to the observed monocyte chemoattractant protein-1 fluctuations and were reduced by febuxostat pretreatment.

Conclusions: Febuxostat exerts preventive effects against reactive oxygen species production and oxidative stress, and might represent a potential treatment for calcium oxalate stones. In the present study, febuxostat downregulated the calcium oxalate monohydrate crystal-induced monocyte chemoattractant protein-1 messenger ribonucleic acid expression.
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http://dx.doi.org/10.1111/iju.14450DOI Listing
March 2021

Potential of an Interorgan Network Mediated by Toxic Advanced Glycation End-Products in a Rat Model.

Nutrients 2020 Dec 29;13(1). Epub 2020 Dec 29.

Department of Urology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.

Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1β and TNF-α is suggested to contribute to the observed changes in kidney gene expression.
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http://dx.doi.org/10.3390/nu13010080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823945PMC
December 2020

EBV-induced gene 3 augments IL-23Rα protein expression through a chaperone calnexin.

J Clin Invest 2020 11;130(11):6124-6140

Department of Immunoregulation, Institute of Medical Science.

Epstein-Barr virus-induced gene 3 (EBI3) is a subunit common to IL-27, IL-35, and IL-39. Here, we explore an intracellular role of EBI3 that is independent of its function in cytokines. EBI3-deficient naive CD4+ T cells had reduced IFN-γ production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-γ production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic Th17 polarizing conditions with IL-23. This is because the induction of expression of one of the IL-23 receptor (IL-23R) subunits, IL-23Rα, but not another IL-23R subunit, IL-12Rβ1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23Rα expression via binding to the chaperone molecule calnexin and to IL-23Rα in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23Rα expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23Rα variant that protects against the development of human colitis, because binding of EBI3 to the variant was reduced. Taken together with the result that EBI3 expression is inducible in T cells, the present results suggest that EBI3 plays a critical role in augmenting IL-23Rα protein expression via calnexin under inflammatory conditions.
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http://dx.doi.org/10.1172/JCI122732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598073PMC
November 2020

The balancing act of Nipponites mirabilis (Nostoceratidae, Ammonoidea): Managing hydrostatics throughout a complex ontogeny.

PLoS One 2020 6;15(8):e0235180. Epub 2020 Aug 6.

Hokkaido University, Shuma-no-kai, Hokkaido, Japan.

Nipponites is a heteromorph ammonoid with a complex and unique morphology that obscures its mode of life and ethology. The seemingly aberrant shell of this Late Cretaceous nostoceratid seems deleterious. However, hydrostatic simulations suggest that this morphology confers several advantages for exploiting a quasi-planktic mode of life. Virtual, 3D models of Nipponites mirabilis were used to compute various hydrostatic properties through 14 ontogenetic stages. At each stage, Nipponites had the capacity for neutral buoyancy and was not restricted to the seafloor. Throughout ontogeny, horizontally facing to upwardly facing soft body orientations were preferred at rest. These orientations were aided by the obliquity of the shell's ribs, which denote former positions of the aperture that were tilted from the growth direction of the shell. Static orientations were somewhat fixed, inferred by stability values that are slightly higher than extant Nautilus. The initial open-whorled, planispiral phase is well suited to horizontal backwards movement with little rocking. Nipponites then deviated from this bilaterally symmetric coiling pattern with a series of alternating U-shaped bends in the shell. This modification allows for proficient rotation about the vertical axis, while possibly maintaining the option for horizontal backwards movement by redirecting its hyponome. These particular hydrostatic properties likely result in a tradeoff between hydrodynamic streamlining, suggesting that Nipponites assumed a low energy lifestyle of slowly pirouetting in search for planktic prey. Each computed hydrostatic property influences the others in some way, suggesting that Nipponites maintained a delicate hydrostatic balancing act throughout its ontogeny in order to facilitate this mode of life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235180PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410299PMC
October 2020

Retinal dysfunction of syphilitic outer retinopathy.

Doc Ophthalmol 2020 10 4;141(2):187-193. Epub 2020 Apr 4.

Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan.

Purpose: We present our findings in two cases of retinal dysfunction caused by syphilitic outer retinopathy. CASE 1: A 59-year-old man visited our clinic complaining of blurred vision in his left eye. Optical coherence tomography (OCT) demonstrated an absence of the ellipsoid zone (EZ) in the left eye. A round yellowish-white lesion was observed in the posterior pole of the left fundus. Fundus autofluorescence (FAF) showed hyperfluorescent areas in the posterior pole of both fundi although no specific ophthalmoscopic findings were seen in the right eye. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were reduced with better preservation of the rod responses. Based on a strong positivity to the rapid plasma reagin (RPR) assay and the Treponema pallidum hemagglutination (TPHA) test, he was diagnosed with syphilitic outer retinopathy and treated with systemic antibiotics. The treatment resulted in a restoration of the retinal structures and cone function. CASE 2: A 47-year-old man was referred to our clinic complaining of reduced vision in both eyes. Although the ocular fundus appeared normal, FAF showed a diffuse hyperfluorescent area in the posterior pole and multiple hyperfluorescent spots. Indocyanine green angiography showed multiple confluent areas of hypofluorescence. OCT demonstrated irregular EZs in both eyes. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were slightly reduced with prolonged implicit times. These findings are comparable to the findings in patients with multiple evanescent white dot syndrome. However, the strong positivity to the RPR and TPHA tests led us to diagnose the patient with outer retinopathy caused by syphilis. Systemic administration of antibiotics resulted in the restoration of the retinal structures and retinal function.

Conclusions: Syphilitic outer retinopathy affected the retinal structures and function that can be restored by antibiotic treatments.
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http://dx.doi.org/10.1007/s10633-020-09763-2DOI Listing
October 2020

High-salt diet promotes crystal deposition through hypertension in Dahl salt-sensitive rat model.

Int J Urol 2019 08 30;26(8):839-846. Epub 2019 Jun 30.

Department of Urology, Kanazawa Medical University, Uchinada, Japan.

Objectives: To study the promotive effect of salt-induced hypertension on crystal deposition and urolithiasis using a salt-sensitive rat hypertension model.

Methods: Hyperoxaluria and hypercalciuria were induced in male Dahl salt-sensitive rats with administration of ethylene glycol and alfacalcidol. Hypertension was induced by a high-salt diet. Eplerenone, a selective mineralocorticoid receptor antagonist, was given. Blood and urine were collected to evaluate renal function, electrolytes and the blood renin-angiotensin-aldosterone system. Renal calcium content was also evaluated. Histological examination, transcriptome analysis with DNA microarray and semiquantitative reverse transcriptase polymerase chain reaction were carried out.

Results: A high-salt diet increased crystal deposition in Dahl salt-sensitive rats with hypertension, and eplerenone administration significantly suppressed it. The mRNA expression profile was associated with crystal formation, growth, adhesion and cellular injury, and it was regulated in the group exposed to a high-salt diet and ethylene glycol.

Conclusions: A high-salt diet has a promotive effect on salt-sensitive hypertension and urolithiasis. This promotive effect can be prevented by eplerenone administration. Hence, salt-sensitive hypertension has promotive effects on crystal deposition in Dahl salt-sensitive rats.
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http://dx.doi.org/10.1111/iju.14035DOI Listing
August 2019

[Follicular lymphoma with nodular lesions mimicking gallbladder carcinoma].

Rinsho Ketsueki 2019 ;60(4):319-325

Department of Hematology, Suita Municipal Hospital.

A 68-year-old female was diagnosed with follicular lymphoma (FL) grade 2, based on the excisional biopsy of her enlarged left cervical lymph node. Positron-emission tomography/computed tomography (PET/CT) revealed the F-fluoro-deoxyglucose-avid lesions in the sigmoid colon and at the fundus of the gallbladder, besides those in the left neck. A sigmoid colon polyp, which was endoscopically resected, proved histologically to be a well- to moderately-differentiated tubular adenocarcinoma with deep invasion into the submucosa. In addition, nodular lesions of the gallbladder were enhanced on dynamic CT, markedly suggesting gallbladder carcinoma. Among FL, colorectal cancer, and presumed gallbladder adenocarcinoma, FL was considered having the lowest priority of treatment because of its indolent nature and low tumor burden. We performed laparoscopic-assisted sigmoid colectomy, followed by gallbladder bed resection on the same day. Unpredictably, gallbladder lesions were histologically revealed to be FL. Often, FL involves extranodal sites such as the gastrointestinal tracts. However, the gallbladder involvement is extremely rare, and preoperative distinction from gallbladder adenocarcinoma remains challenging to date; this report discusses its characteristics along with the literature review. Furthermore, our case, in which another malignant neoplasm coexisted, needed histological identification of the gallbladder lesions to ascertain the therapeutic strategy.
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http://dx.doi.org/10.11406/rinketsu.60.319DOI Listing
August 2019

[CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS].

Nihon Hinyokika Gakkai Zasshi 2019 ;110(3):168-176

Department of Urology, Kanazawa Medical University.

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.
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http://dx.doi.org/10.5980/jpnjurol.110.168DOI Listing
January 2019

[Systemic lupus erythematosus with marked eosinophilia and clinical features mimicking TAFRO syndrome].

Rinsho Ketsueki 2018;59(6):688-694

Department of Hematology, Suita Municipal Hospital.

A 76-year-old woman was referred to our hospital because of fever, hemorrhagic skin lesion with pruritus, and severe thrombocytopenia. Anemia; marked eosinophilia; and elevated ALP, CRP, and soluble IL-2 receptor levels were observed on admission. Both anti-nuclear antibody and Coombs tests were positive. Computed tomography revealed bilateral pleural effusion, ascites, abdominal lymphadenopathy, and mild hepatosplenomegaly. A thorough examination for the initial differential diagnoses excluded the possibility of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement, infectious diseases, and eosinophilic granulomatosis with polyangiitis. Remaining possibilities included angioimmunoblastic T-cell lymphoma (AITL) and systemic inflammatory disorders. Although AITL was plausible, there was no histological evidence to support the diagnosis. The patient was then administered prednisolone alone, which led to a lasting resolution of her symptoms. The atypical AITL course raised the suspicion of a misdiagnosis; thus the possibility of an inflammatory disease was reconsidered. TAFRO syndrome was suspected owing to its characteristic clinical features (thrombocytopenia, anasarca, fever and organomegaly). Since a definitive diagnosis required the exclusion of systemic lupus erythematosus (SLE), anti-double-stranded DNA antibody was tested in the initial frozen serum sample. An unexpected positive result led to the final diagnosis of SLE. Here, we report a rare case of SLE lacking typical symptoms and exhibiting various hematological abnormalities, such as eosinophilia.
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http://dx.doi.org/10.11406/rinketsu.59.688DOI Listing
July 2019

[Neutrophil recovery by eltrombopag treatment in a patient with adult-onset autoimmune neutropenia and immune thrombocytopenia].

Rinsho Ketsueki 2018;59(3):310-314

Department of Hematology, Suita Municipal Hospital.

Adult-onset autoimmune neutropenia (AIN) is rarely self-limiting, unlike infant-onset AIN. Although several therapeutic agents have been reported, including corticosteroids, more effective treatment options may exist. Here, we describe neutrophil recovery by eltrombopag in a 52-year-old male AIN patient with immune thrombocytopenia (ITP) who was referred to our hospital with severe neutropenia. Within a year of referral, he developed moderate thrombocytopenia. He was diagnosed with AIN and concurrent ITP, based on the detection of antineutrophil antibodies and bone marrow aspiration, respectively. Further platelet count reduction and the appearance of purpura prompted an initial treatment of 0.5 mg/kg prednisolone. Thrombocytopenia remission was prompt but transient, with platelet counts rapidly declining before initiating prednisolone tapering. Similarly, absolute neutrophil counts (ANCs), after a shorter recovery period, returned to the baseline level below 2×10/l. Further platelet reduction was prevented by eltrombopag administration. Intriguingly, the ANCs recovered following platelet recovery and remained above 5×10/l for > three months despite prednisolone dosage tapering. To our knowledge, this is the first report describing the effectiveness of eltrombopag in AIN.
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http://dx.doi.org/10.11406/rinketsu.59.310DOI Listing
July 2019

[Clinical Study on the Efficacy and Continuous Docetaxel Based Chemotherapy Treatment for Castration-Resistant Prostate Cancer].

Hinyokika Kiyo 2017 Sep;63(9):351-357

The Department of Urology, Kanazawa Medical University.

We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level. Adverse effect of grade 3 consisted of neutropenia in 29.7% and leukocytopenia in 10.8%. The median number of treatment cycles was 11.7 courses. The patients were divided into two groups ; the first group comprised of 26 patients who received short-term DOC therapy (≤10 cycles) and the second group comprised of 11 patients who received long-term DOC therapy (≥11 cycles). The 1-year survival rate was 59 and 100% for the short-term and long-term groups, respectively. Long-term treatment was related to pretreatment PSA nadir, time to progression of CRPC and serum lactate dehydrogenase level.
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http://dx.doi.org/10.14989/ActaUrolJap_63_9_351DOI Listing
September 2017

Stepwise Total Aortic Repairs With Fenestrated Endografts in a Patient With Loeys-Dietz Syndrome.

Ann Thorac Surg 2017 Jul;104(1):e39-e42

Department of Cardiovascular Surgery, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.

Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder (CTD) caused by mutations in the gene encoding transforming growth factor-β receptors Ⅰ and Ⅱ. Patients with LDS manifest spontaneous aneurysms and dissections of the aorta and peripheral artery. We report a successful treatment with a hybrid endovascular repair for a rapidly expanding thoracoabdominal aneurysm in a 41-year-old woman affected by LDS. To overcome the difficulties of anatomical and surgical repair, we applied an original strategy using surgeon-modified fenestrated endografts.
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http://dx.doi.org/10.1016/j.athoracsur.2017.02.017DOI Listing
July 2017

THE EFFECT OF RADIATION THERAPY FOR BONE METASTASIS IN URINARY ORGAN CANCER.

Nihon Hinyokika Gakkai Zasshi 2016 ;107(1):7-12

Department of Urology, Kanazawa Medical University.

(Objective) Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. (Results) Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. (Conclusion) This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer.
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http://dx.doi.org/10.5980/jpnjurol.107.7DOI Listing
August 2018

Suture pattern formation in ammonites and the unknown rear mantle structure.

Sci Rep 2016 09 19;6:33689. Epub 2016 Sep 19.

Graduate School of Frontier Bioscience, Osaka University, Yamada 1-3, Suita, Osaka 565-0871, Japan.

Ammonite shells have complex patterns of suture lines that vary across species. The lines are formed at the intersection of the outer shell wall and the septa. The wavy septa can form if the rear mantle of the ammonite, which functions as the template, has a complex shape. Previous hypotheses assumed that the rear mantle is like a flexible membrane that can be folded by some physical force. The elucidation of the mechanism of septa formation requires that the detailed shape of the septa should be known. We developed a new protocol of X-ray micro-computed tomography (CT) and obtained high-resolution three-dimensional (3D) images of the septa of the Upper Cretaceous ammonite Damesites cf. damesi. The obtained image suggested that the wavy and branched structures of the rear mantle grew autonomously. We found that some extant sea slugs have branched structures and showed similar shape and growth sequence as those in fossils, suggesting that the mantle of molluscs basically has the potential to form branched projections. Based on the characteristics of the obtained 3D structure, we explain how ammonites might have formed the complex suture patterns.
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http://dx.doi.org/10.1038/srep33689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027383PMC
September 2016

A Permanent Epicardial Pacemaker Lead That Penetrated the Esophageal Wall 26 years After Implantation.

Ann Thorac Surg 2016 Sep;102(3):e185-e186

Department of Surgery, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.

We treated a patient in whom a permanent epicardial pacemaker lead penetrated the esophageal wall 26 years after the index pacemaker implantation. A 28-year-old man with loss of appetite and weight loss underwent upper gastrointestinal endoscopy and was found to have a foreign body protruding into the esophagus. Computed tomography revealed an epicardial lead penetrating the esophageal wall. He had undergone pacemaker implantation with permanent epicardial leads when he was 2 years old. The lead was surgically removed.
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http://dx.doi.org/10.1016/j.athoracsur.2016.02.022DOI Listing
September 2016

Movement Patterns and Residency of the Critically Endangered Horseshoe Crab Tachypleus tridentatus in a Semi-Enclosed Bay Determined Using Acoustic Telemetry.

PLoS One 2016 10;11(2):e0147429. Epub 2016 Feb 10.

Institute for East China Sea Research, Graduate School of Fisheries and Environmental Sciences, Nagasaki University, Nagasaki, Japan.

The horseshoe crab Tachypleus tridentatus is critically endangered in Japan due to rapidly decreasing numbers resulting from the loss of tidal flats and sandy beaches, and the deterioration of coastal environments. We monitored the year-round migratory patterns and residency of this species in a coastal embayment at Tsuyazaki, Japan, using acoustic telemetry. Total 20 adult crabs (15 males and 5 females) were tagged with ultrasonic transmitters and tracked during two periods (2006-2008; n = 10 and 2007-2009; n = 10). Adult crabs were more active during periods of higher water temperatures and their activity peaked in July, during the spawning period. Water temperature appeared to be one of the key factors influencing the movement patterns for the species. Moreover, the crabs tended to be more active at night than in the day. The nocturnal activity pattern was clearly evident before and during the reproductive period (May-August). Tracking data also showed that one pair-bond was maintained for a maximum of 17 days after the pair-bonded female had spawned. Overall, 11 males (73% of 15 individuals) remained in the bay area over winter, whereas three females (60% of 5 individuals) overwintered outside of the bay. Telemetry data showed that over 60% (13 of 20) of tagged crabs overwintered within the bay where there are sandy beaches, mudflats, and scattered seagrass beds. This year-round residence by adult T. tridentatus in the bay area identifies it as a critical habitat for the management of this species, regardless of life-stage. Not only is it a comprehensive management strategy that effectively reflects this species' habitat use patterns but also its implementation, such as the establishment of a protected area, would contribute to its conservation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147429PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749169PMC
July 2016

Tetraspanin 3c requirement for pigment cell interactions and boundary formation in zebrafish adult pigment stripes.

Pigment Cell Melanoma Res 2014 Mar;27(2):190-200

Skin pigment pattern formation in zebrafish requires pigment-cell autonomous interactions between melanophores and xanthophores, yet the molecular bases for these interactions remain largely unknown. Here, we examined the dali mutant that exhibits stripes in which melanophores are intermingled abnormally with xanthophores. By in vitro cell culture, we found that melanophores of dali mutants have a defect in motility and that interactions between melanophores and xanthophores are defective as well. Positional cloning and rescue identified dali as tetraspanin 3c (tspan3c), encoding a transmembrane scaffolding protein expressed by melanophores and xanthophores. We further showed that dali mutant Tspan3c expressed in HeLa cell exhibits a defect in N-glycosylation and is retained inappropriately in the endoplasmic reticulum. Our results are the first to identify roles for a tetraspanin superfamily protein in skin pigment pattern formation and suggest new mechanisms for the establishment and maintenance of zebrafish stripe boundaries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988474PMC
http://dx.doi.org/10.1111/pcmr.12192DOI Listing
March 2014

Ectopic cervical thymoma accompanied by Good's syndrome.

Ann Thorac Cardiovasc Surg 2014 31;20 Suppl:531-4. Epub 2013 Jan 31.

Department of General Thoracic Surgery, Osaka University Grad uate School of Medicine, Osaka, Japan.

Ectopic cervical thymoma (ECT) is a rare tumor that is frequently misdiagnosed as a thyroid tumor or other malignancy. A 34-year-old male with a right palpable neck mass had been mistakenly diagnosed with T-cell lymphoblastic lymphoma even after an open biopsy. The atypical clinical course, including hypogammaglobulinemia, led us to the correct diagnosis; ECT accompanied by Good's syndrome (GS). After the intravenous infusion of gammaglobulin, tumor resection and a subsequent video-assisted thoracoscopic extended thymectomy were performed. The final diagnosis was type AB thymoma, Masaoka stage I. This report is, to the best of our knowledge, the first description of this extremely rare combination.
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http://dx.doi.org/10.5761/atcs.cr.12.02027DOI Listing
October 2015

Endovascular aneurysm repair using the periscope graft technique for thoracic aortic anastomotic pseudoaneurysm.

Interact Cardiovasc Thorac Surg 2013 Apr 19;16(4):553-5. Epub 2012 Dec 19.

Department of Cardiovascular Surgery, Saiseikai Utsunomiya Hospital, Takebayashi, Utsunomiya, Tochigi, Japan.

Replacement of an artificial graft in a redo lateral thoracotomy is extremely difficult with a high risk of lung injury. Endovascular intervention may be an ideal option in such conditions, as in the following case. A 75-year old man with a history of coronary artery bypass graft surgery developed a proximal anastomotic pseudoaneurysm 1 year after undergoing artificial proximal descending aorta replacement surgery. Thoracic endovascular aneurysm repair was performed successfully using the periscope graft technique to preserve the flow into the left subclavian artery from the distal side of the aortic stent graft. Since the patient had coronary artery bypass grafting, debranching of the left subclavian artery was considered too risky. Using the periscope graft technique, the pseudoaneurysm was successfully repaired preserving the left subclavian artery patency, thus obviating a side-to-side subclavian artery crossover bypass.
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http://dx.doi.org/10.1093/icvts/ivs519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598029PMC
April 2013

Combined use of an epidural cooling catheter and systemic moderate hypothermia enhances spinal cord protection against ischemic injury in rabbits.

J Thorac Cardiovasc Surg 2013 Sep 13;146(3):696-701. Epub 2012 Dec 13.

Department of Cardiovascular Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.

Background: Epidural placement of a cooling catheter can protect against ischemic spinal cord injury. With the use of rabbits, we investigated whether this epidural cooling technique, when combined with systemic moderate hypothermia, can protect the spinal cord against ischemic metabolic stress.

Methods: New Zealand white rabbits (n = 28) were assigned to 1 of 4 different groups. Animals underwent abdominal aortic occlusion for 30 minutes using a 3F balloon catheter. Group 1 (n = 7) underwent epidural cooling by the catheter and systemic moderate hypothermia (35 °C) induced with a cooling blanket. Group 2 (n = 7) underwent epidural cooling under systemic normothermia (38.5 °C). Group 3 (n = 7) underwent systemic moderate hypothermia (35 °C) without epidural cooling. Group 4 (n = 7) underwent neither epidural nor blanket cooling as a negative control. Neurologic status of their hind limbs was graded according to the modified Tarlov scale at 1, 2, and 7 days after surgery.

Results: During infrarenal aortic ischemia, epidural temperature was significantly lower in group 1 (18.5 °C ± 0.8 °C) than in group 2 (28.6 °C ± 1.0 °C; P = .0001), group 3 (34.2 °C ± 0.06 °C; P = .0001), or group 4 (38.5 °C ± 0.2 °C; P = .0001). Hind limb function recovery was greater in group 1 (mean Tarlov score, 4.9 ± 0.057) than in group 2 (2.6 ± 0.3; P = .0028), group 3 (2.1 ± 0.34; P = .0088), or group 4 (0.0 ± 0.0; P = .0003).

Conclusions: Epidural cooling catheter combined with systemic moderate hypothermia produced additive cooling ability and protected the spinal cord against ischemia in rabbits more effectively than either intervention alone.
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http://dx.doi.org/10.1016/j.jtcvs.2012.11.040DOI Listing
September 2013

Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

PLoS Genet 2012 16;8(8):e1002899. Epub 2012 Aug 16.

Department of Biology, University of Washington, Seattle, Washington, United States of America.

The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.
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http://dx.doi.org/10.1371/journal.pgen.1002899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420941PMC
December 2012

Brain swelling in acute superior vena cava syndrome due to aortic dissection: unusual and lethal manifestation aggravated by induction of general anesthesia.

Gen Thorac Cardiovasc Surg 2012 Dec 26;60(12):815-7. Epub 2012 May 26.

Division of Cardiovascular Surgery, Saiseikai Utsunomiya Hospital, 911-1 Takebayashi-cho, Utsunomiya, Tochigi, 321-0974, Japan.

A 32-year-old woman with Marfan syndrome experienced acute superior vena cava syndrome due to aortic dissection. The patient had previously undergone a Bentall operation. The aneurysm from the ascending to the transverse aorta compressed the superior vena cava, the right pulmonary artery, and the trachea. The rare and life-threatening neurological complication in this patient may have been related to brain edema, which was revealed by preoperative computed tomography. The induction of general anesthesia aggravated the symptoms of the superior vena cava syndrome and led to a fatal condition. Additional cannulation in the right subclavian vein was mandatory to alleviate the symptoms because the venous drainage from the upper half of the body created only by the femorofemoral bypass was not adequate. Total arch replacement was performed. The postoperative course was uneventful.
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http://dx.doi.org/10.1007/s11748-012-0079-2DOI Listing
December 2012

[Determination of the optimal ROI setting position of the input function for the ⁹⁹mTc-ethyl cysteinate dimmer brain uptake ratio method].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2012 ;68(3):269-76

Graduate School of Health Sciences, Kumamoto University.

Determination of the input function for the (99m)Tc-ethyl cysteinate dimmer brain uptake ratio ((99m)Tc-ECD BUR) method as a non-invasive quantitative measurement of cerebral blood flow measurement is of critical importance in order to improve the accuracy of this method. The input functions were experimentally obtained by setting the regions of interest (ROIs) in the ascending aorta, aortic arch, and descending aorta on the 49 chest RI-angio images. rCBFs by the BUR method with 3 input functions of the 6 cases were compared with those by the (123)I-iodoamphetamine (IMP) continuous arterial blood sampling method in order to determine the best location for the ROI of the input function. The input function of the ascending aorta was higher than those of the aortic arch and the descending aorta. The input functions of the aortic arch and the descending aorta decreased due to the origin of the three branches of the right brachiocephalic artery, left subclavian artery, and left common carotid artery. A good correlation was found in the regional cerebral blood flow (rCBF) values between the (123)I-IMP continuous arterial blood sampling method and the (99m)Tc-ECD BUR method with the input function of the ascending aorta. Therefore, the ascending aorta is the best location for the ROI of the input function for the (99m)Tc-ECD BUR method.
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http://dx.doi.org/10.6009/jjrt.2012_jsrt_68.3.269DOI Listing
August 2012

Improvement of the (99m)Tc-ECD brain uptake ratio (BUR) method for measurement of cerebral blood flow.

Ann Nucl Med 2012 May 18;26(4):351-8. Epub 2012 Feb 18.

Department of Medical Imaging, Faculty of Life Science, Kumamoto University, Kuhonji 4-24-1, Kumamoto, 862-0796, Japan.

Objective: The brain uptake ratio (BUR) method for the (99m)Tc-ECD SPECT, a non-invasive measurement method of rCBF, has been used in clinical practice in Japan, because it is simple to use. However, the accuracy of this method is limited, as it has problems in the determination of input function and the regression equation. The purpose of this study is to improve the BUR method by reconstructing the determination process of the input function and regression equation based on measurement of the rCBF by H (2) (15) O PET.

Method: The input function was obtained by setting the region of interest on the ascending aorta instead of the aortic arch. The 3DSRT algorithm was used to obtain the anatomically standardized rCBF, and developed a semi-automatic analyzing software using C++ in order to stabilize the repeatability of the improved BUR (IBUR) method. The regression equation for the IBUR method was obtained by the H (2) (15) O PET rCBFs in 15 patients with the arterial blood sampling method. All the measurements in this study were performed with the patient in the resting state.

Result: A good correlation was observed between the rCBF values measured by H (2) (15) O PET and the regional BURs measured by the IBUR method (r = 0.86, p < 0.0001). The rCBF values were calculated for only 5 min using a semi-automatic analyzing software.

Conclusion: The BUR method was improved by changing the location of the input function from the aortic arch to the ascending aorta based on arterial blood flow dynamics, and reconstructing regression equation based on the rCBF values obtained using H (2) (15) O PET. This finding indicates the potential clinical usefulness of this method.
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http://dx.doi.org/10.1007/s12149-012-0582-7DOI Listing
May 2012
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