132 results on '"Ishikawa, C."'
Search Results
2. Two‐Year Follow‐Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease
- Author
-
Ito, D., Ishikawa, C., Jeffery, N.D., Ono, K., Tsuboi, M., Uchida, K., Yamato, O., and Kitagawa, M.
- Subjects
MRS ,lcsh:Veterinary medicine ,Neurology ,nervous system ,GM2 gangliosidosis ,Lysosomal storage diseases ,lcsh:SF600-1100 ,Case Report ,SMALL ANIMAL ,Case Reports ,MRI - Abstract
A 13‐month‐old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient β‐N‐acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2‐weighted and fluid‐attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N‐acetylaspartate, and glycine‐myo‐inositol and lactate‐alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.
- Published
- 2018
3. Single-pole/TMR heads for 140-Gb/[in.sup.2] perpendicular recording
- Author
-
Nakamoto, K., Okada, T., Watanabe, K., Hoshiya, H., Yoshida, N., Kawato, Y., Hatatani, M., Meguro, K., Okada, Y., Kimura, H., Mochizuki, M., Kusukawa, K., Ishikawa, C., and Fuyama, M.
- Subjects
Electromagnetism -- Research ,Business ,Electronics ,Electronics and electrical industries - Abstract
Single-pole writers and tunneling magnetoresistive (TMR) readers for 140-Gb/[in.sup.2] perpendicular recording were fabricated and their recording performance was tested. Data erasure, which is observed as write instability in a repeated read-write operation, can be suppressed by combining a laminated pole and low throat height. Fe--Co/Ni--Cr laminated film was used to reduce the remanent magnetization of the main pole after patterning. Narrow track writers with a 120-nm-wide trapezoidal pole showed a good write ability of 30 dB or more in overwrite for media with high coercivity of up to 7 kOe. Also, negligibly small skew writing was confirmed. TMR heads with a sensor width of 85 nm and a head resistance of 250 [ohm] showed approximately 30 dB of head signal-to-noise ratio (SNR). A potentially higher SNR with a higher operating voltage was suggested from a measured output versus sensing current curve. Calculations showed that the side reading was suppressed in a side-shielded design. A 10% amplitude width of the microtrack profile of a 100-nm-wide reader was reduced from 198 to 162 nm by applying the side shields. Index Terms--Laminated pole, perpendicular recording, pole erasure, side shield, single-pole writer, skew writing, TMR heads.
- Published
- 2004
4. Note on a Gigantic Squid obtained from the Stomach of a Sperm Whale
- Author
-
Ishikawa, C, Wakiya, Yôjirô, and BioStor
- Published
- 1914
5. On a New Species of Moroteuthis from the Bay of Sagami, M. Lönnbergii
- Author
-
Ishikawa, C, Wakiya, Y, and BioStor
- Published
- 1914
6. Einige bermerkungen uber den leuchtenden Tintenfisch, Watasea n. gen. (Abraliopsis der Autoren) scintillans Berry, aus Japan
- Author
-
Ishikawa, C and BioStor
- Published
- 1913
7. Über eine neue Art von Enoploteuthis, Enoploteuthis chunii spec. nov. aus Uwodu, Japanisches Meer
- Author
-
Ishikawa, C and BioStor
- Published
- 1914
8. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway
- Author
-
Hasegawa, H, Yamada, Y, Tsukasaki, K, Mori, N, Tsuruda, K, Sasaki, D, Usui, T, Osaka, A, Atogami, S, Ishikawa, C, Machijima, Y, Sawada, S, Hayashi, T, Miyazaki, Y, and Kamihira, S
- Published
- 2011
- Full Text
- View/download PDF
9. On the formation of eggs in the testis of Gebia major, De Haan
- Author
-
Ishikawa, C and BioStor
- Published
- 1891
10. SAT-206 EFFECT OF FRUTOOLIGOSACCHARIDE ON ENDOTHELIAL FUNCTION IN CKD PATIENTS: A RANDOMIZED CONTROLLED TRIAL
- Author
-
ARMANI, R., primary, Ishikawa, C., additional, Hong, V., additional, Bortolotto, L.A., additional, Cassiolatto, J.L., additional, Klassen, A., additional, Cuppari, L., additional, and Canziani, M.E., additional
- Published
- 2019
- Full Text
- View/download PDF
11. Atypical tumour-like involvement of the colon in Henoch-Schonlein purpura successfully treated with the administration of factor XIII
- Author
-
Ando, K., primary, Fujiya, M., additional, Sugiyama, R., additional, Nata, T., additional, Nomura, Y., additional, Ueno, N., additional, Kashima, S., additional, Ishikawa, C., additional, Inaba, Y., additional, Ito, T., additional, Moriichi, K., additional, Okamoto, K., additional, Ikuta, K., additional, Watari, J., additional, Mizukami, Y., additional, and Kohgo, Y., additional
- Published
- 2011
- Full Text
- View/download PDF
12. Atypical tumour-like involvement of the colon in secondary systemic amyloidosis which vanished after 1 month of observation
- Author
-
Ando, K., primary, Fujiya, M., additional, Ito, T., additional, Sugiyama, R., additional, Nata, T., additional, Nomura, Y., additional, Ueno, N., additional, Kashima, S., additional, Ishikawa, C., additional, Inaba, Y., additional, Moriichi, K., additional, Okamoto, K., additional, Ikuta, K., additional, Mizukami, Y., additional, Tokusashi, Y., additional, Miyokawa, N., additional, Watari, J., additional, and Kohgo, Y., additional
- Published
- 2011
- Full Text
- View/download PDF
13. Activation of AID by human T-cell leukemia virus Tax oncoprotein and the possible role of its constitutive expression in ATL genesis
- Author
-
Ishikawa, C., primary, Nakachi, S., additional, Senba, M., additional, Sugai, M., additional, and Mori, N., additional
- Published
- 2010
- Full Text
- View/download PDF
14. Capsule endoscopy is a feasible procedure for identifying a Diphyllobothrium nihonkaiense infection and determining the indications for vermifuge treatment
- Author
-
Nomura, Y., primary, Fujiya, M., additional, Ito, T., additional, Ando, K., additional, Sugiyama, R., additional, Nata, T., additional, Ueno, N., additional, Kashima, S., additional, Ishikawa, C., additional, Inaba, Y., additional, Moriichi, K., additional, Okamoto, K., additional, Yanagida, T., additional, Ito, A., additional, Ikuta, K., additional, Watari, J., additional, Mizukami, Y., additional, and Kohgo, Y., additional
- Published
- 2010
- Full Text
- View/download PDF
15. Aberrant expression of the transcription factor Twist in adult T-cell leukemia
- Author
-
Tanji, H., primary, Ishikawa, C., additional, Sawada, S., additional, Nakachi, S., additional, Takamatsu, R., additional, Matsuda, T., additional, Okudaira, T., additional, Uchihara, J.-N., additional, Ohshiro, K., additional, Tanaka, Y., additional, Senba, M., additional, Uezato, H., additional, Ohshima, K., additional, Duc Dodon, M., additional, Wu, K.-J., additional, and Mori, N., additional
- Published
- 2010
- Full Text
- View/download PDF
16. A case of small cell carcinoma of the oesophagus treated with endoscopic mucosal resection who remained in clinical remission for 18 months: its endoscopic features with specific light spectra
- Author
-
Nata, T., primary, Fujiya, M., additional, Tanabe, H., additional, Ueno, N., additional, Konno, Y., additional, Ishikawa, C., additional, Inaba, Y., additional, Ito, T., additional, Sato, R., additional, Moriichi, K., additional, Okamoto, K., additional, Maemoto, A., additional, Mizukami, Y., additional, Watari, J., additional, Ashida, T., additional, and Kohgo, Y., additional
- Published
- 2009
- Full Text
- View/download PDF
17. The p75 Neurotrophin Receptor Promotes Amyloid- (1-42)-Induced Neuritic Dystrophy In Vitro and In Vivo
- Author
-
Knowles, J. K., primary, Rajadas, J., additional, Nguyen, T.-V. V., additional, Yang, T., additional, LeMieux, M. C., additional, Vander Griend, L., additional, Ishikawa, C., additional, Massa, S. M., additional, Wyss-Coray, T., additional, and Longo, F. M., additional
- Published
- 2009
- Full Text
- View/download PDF
18. Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure
- Author
-
Tsutamoto, T., primary, Tanaka, T., additional, Sakai, H., additional, Ishikawa, C., additional, Fujii, M., additional, Yamamoto, T., additional, and Horie, M., additional
- Published
- 2007
- Full Text
- View/download PDF
19. Side-Shielded Tunneling Magnetoresistive Read Head for High-Density Recording
- Author
-
Haginoya, C., primary, Hatatani, M., additional, Meguro, K., additional, Ishikawa, C., additional, Yoshida, N., additional, Kusukawa, K., additional, and Watanabe, K., additional
- Published
- 2004
- Full Text
- View/download PDF
20. Single-Pole/TMR Heads for 140->tex<$hboxGb/in^2$>/tex<Perpendicular Recording
- Author
-
Nakamoto, K., primary, Okada, T., additional, Watanabe, K., additional, Hoshiya, H., additional, Yoshida, N., additional, Kawato, Y., additional, Hatatani, M., additional, Meguro, K., additional, Okada, Y., additional, Kimura, H., additional, Mochizuki, M., additional, Kusukawa, K., additional, Ishikawa, C., additional, and Fuyama, M., additional
- Published
- 2004
- Full Text
- View/download PDF
21. Seasonal and diurnal patterns of soil water potential in the rhizosphere of blue oaks: evidence for hydraulic lift
- Author
-
Ishikawa, C. Millikin, primary and Bledsoe, C.S., additional
- Published
- 2000
- Full Text
- View/download PDF
22. A new method of calculating the medium field and the demagnetizing field for MR heads
- Author
-
Suzuki, Y., primary and Ishikawa, C., additional
- Published
- 1998
- Full Text
- View/download PDF
23. Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung
- Author
-
Iigo, M, primary, Nakagawa, T, additional, Ishikawa, C, additional, Iwahori, Y, additional, Asamoto, M, additional, Yazawa, K, additional, Araki, E, additional, and Tsuda, H, additional
- Published
- 1997
- Full Text
- View/download PDF
24. Furthur Observations on the Nuclear Division of Noctiluca
- Author
-
Ishikawa, C.
- Subjects
483.13 ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING - Abstract
application/pdf
- Published
- 1900
25. II. Intravenous Set With Two-way Stopcock
- Author
-
Ishikawa C
- Subjects
Psychophysiologic Disorders ,business.industry ,Stress (linguistics) ,Medicine ,General Medicine ,business ,General Nursing ,Clinical psychology - Published
- 1939
26. Effects of Chronic Barley Consumption on Upper Respiratory Tract Symptoms in Japanese Healthy Adults: A Randomized, Parallel-Group, Controlled Trial.
- Author
-
Araki R, Ishikawa C, Kawasaki T, Kobori T, Shoji T, and Takayama Y
- Subjects
- Humans, Female, Male, Adult, Japan, beta-Glucans administration & dosage, Middle Aged, Sneezing, Young Adult, Cooking methods, Affect, Respiratory Tract Diseases prevention & control, East Asian People, Hordeum
- Abstract
β-(1,3/1,4)-glucan is a major component of cereal grains, such as oats and barley. In this study, we investigated the effects of cooked waxy barley, which contains β-(1,3/1,4)-glucan, on upper respiratory tract physical symptoms and mood status by performing a randomized, parallel-group, comparative trial. The primary outcome was assessed using the Wisconsin Upper Respiratory Symptom Survey-21 and Profile of Mood States second edition. Twenty-seven healthy Japanese adult participants were supplemented with 100 g of cooked waxy barley (containing 1.8 g of β-glucan) or 100 g of cooked white rice daily for 8 weeks. Participants receiving cooked waxy barley reported a reduction in cumulative days of sneezing ( p < 0.05) and feeling tired ( p < 0.0001) compared with the control group. After the intervention period, there were significantly less severe nasal symptoms, such as runny nose, plugged nose, and sneezing ( p < 0.05), and a significantly greater reduction of the Tension-Anguish score ( p < 0.05) in the barley group than in the control group. This study suggests that supplementation of cooked waxy barley containing β-(1,3/1,4)-glucan prevents or alleviates nasal upper respiratory tract symptoms and improves mood status. The findings of this study should be confirmed by double-blind trials with a larger number of participants.
- Published
- 2024
- Full Text
- View/download PDF
27. A Data-Driven Approach to Sugarcane Breeding Programs with Agronomic Characteristics and Amino Acid Constituent Profiling.
- Author
-
Ishikawa C, Date Y, Umeda M, Tarumoto Y, Okubo M, Morimitsu Y, Tamura Y, Nishiba Y, and Ono H
- Abstract
Sugarcane ( Saccharum spp. hybrids) and its processed products have supported local industries such as those in the Nansei Islands, Japan. To improve the sugarcane quality and productivity, breeders select better clones by evaluating agronomic characteristics, such as commercially recoverable sugar and cane yield. However, other constituents in sugarcane remain largely unutilized in sugarcane breeding programs. This study aims to establish a data-driven approach to analyze agronomic characteristics from breeding programs. This approach also determines a correlation between agronomic characteristics and free amino acid composition to make breeding programs more efficient. Sugarcane was sampled in clones in the later stage of breeding selection and cultivars from experimental fields on Tanegashima Island. Principal component analysis and hierarchical cluster analysis using agronomic characteristics revealed the diversity and variability of each sample, and the data-driven approach classified cultivars and clones into three groups based on yield type. A comparison of free amino acid constituents between these groups revealed significant differences in amino acids such as asparagine and glutamine. This approach dealing with a large volume of data on agronomic characteristics will be useful for assessing the characteristics of potential clones under selection and accelerating breeding programs.
- Published
- 2024
- Full Text
- View/download PDF
28. Oncostatin M's Involvement in the Pathogenesis of Chronic Rhinosinusitis: Focus on Type 1 and 2 Inflammation.
- Author
-
Ishikawa C, Takeno S, Okamoto Y, Kawasumi T, Kakimoto T, Takemoto K, Nishida M, Ishino T, Hamamoto T, Ueda T, and Tanaka A
- Abstract
Objectives: The cytokine oncostatin M (OSM) elicits pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is unclear how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in CRS patients' sinonasal specimens, and we compared the results with a panel of inflammatory cytokine levels and clinical features., Patients and Methods: We classified CRS patients as eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis phenotypic criteria and compared their cases with those of 20 control subjects. We also examined OSM's stimulatory effects on cytokine receptor expression levels using the human bronchial epithelium cell line BEAS-2B., Results: RT-PCR showed that the OSM mRNA levels were significantly increased in the CRS patients' ethmoid sinus mucosa. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMRβ, IL-1R1, and IL-13Ra mRNA levels., Conclusions: OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.
- Published
- 2023
- Full Text
- View/download PDF
29. Building Authentic Science Experiences: Students' Perceptions of Sequential Course-Based Undergraduate Research.
- Author
-
Von der Mehden BM, Pennino EM, Fajardo HL, Ishikawa C, and McDonald KK
- Subjects
- Humans, Cross-Sectional Studies, Curriculum, Research Design, Students, Laboratories
- Abstract
Course-based Undergraduate Research Experiences (CUREs) are attractive solutions for scaling undergraduate research experiences at primarily undergraduate teaching institutions, where resources for faculty research activities can be limited. The Sustainable Interdisciplinary Research to Inspire Undergraduate Success (SIRIUS) project is a unique program that integrates CUREs, coordinated around a local real-world problem, throughout a biology department's curricula. The CUREs are scaffolded to provide all biology majors with multiple opportunities to engage in scientific investigations as they advance through introductory, intermediate, and advanced courses. In this mixed methods, cross-sectional study, we explore students' perceptions of the authenticity of their experiences as they progress through the SIRIUS CUREs. Triangulated data collected from two instruments indicated that students in advanced courses recognized more involvement in research activities and perceived greater authenticity in the science they were performing compared with introductory and intermediate students. Intermediate and advanced students perceived more opportunities for independence; however, experiences with failure and the influence these experiences had on the perceptions of authenticity was primarily observed with advanced students. This study contributes to the growing literature on CUREs with a focus on students from a primarily undergraduate institution with multiple minority-serving designations.
- Published
- 2023
- Full Text
- View/download PDF
30. A Rare Presentation of Pseudo-Pneumoperitoneum Secondary to Chilaiditi Sign and Chilaiditi Syndrome in Two Pre-adolescent Females: A Case Series.
- Author
-
Vazquez V, Jones N, Ishikawa C, Watal P, and Ali S
- Abstract
Chilaiditi sign is defined as the interposition of the colon or small intestine between the liver and the right diaphragm in the absence of symptoms. Chilaiditi syndrome refers to the condition where the Chilaiditi sign is associated with symptoms including abdominal pain. In this series, we present the cases of two pre-pubescent patients with these rare conditions. A 10-year-old female with a history of autism, IgA deficiency, and constipation presented for gastrointestinal studies due to weight loss and constipation. An abdominal X-ray revealed bowel gas under the right hemidiaphragm and colonic interposition between the diaphragm and the liver, raising concerns for the Chilaiditi sign. She underwent a bowel cleanout, with studies revealing colonic dysmotility and compartmentalization of the sigmoid colon and rectum with the absence of coloanal reflex. A nine-year-old female with a history of constipation, developmental delay, and hypotonia presented with abdominal pain, vomiting, constipation, and decreased appetite. She also manifested tachypnea, abdominal distension, and abdominal tenderness, with an abdominal X-ray revealing a dilated colon interposed between the liver and diaphragm, confirming Chilaiditi syndrome. Prior gastrointestinal studies showed dilated and redundant sigmoid colon and dyssynergia. The treatment entailed rectal irrigations and catheter decompression, which led to the improvement of symptoms. Conservative treatment is the treatment of choice for patients with Chilaiditi sign or Chilaiditi syndrome. It is important to distinguish Chilaiditi syndrome, a common cause of pseudo-pneumoperitoneum, from true pneumoperitoneum, as this diagnosis warrants immediate surgical intervention. Surgical treatment is indicated when there are signs of bowel obstruction or ischemia and for cases with recurrent Chilaiditi syndrome. Raising awareness about this condition is important to reduce the incidence of misdiagnosed surgical emergencies and resulting exploratory surgeries, as well as to avoid high-risk colonoscopies. Chilaiditi sign and Chilaiditi syndrome are relatively uncommon entities, and their prevalence is very rare in the pediatric population. Hence, we believe this case series will contribute to providing clinical awareness of these major complications and avoiding invasive interventions due to the inaccurate diagnosis of these conditions as pneumoperitoneum., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vazquez et al.)
- Published
- 2023
- Full Text
- View/download PDF
31. Oncostatin M suppresses IL31RA expression in dorsal root ganglia and interleukin-31-induced itching.
- Author
-
Suehiro M, Numata T, Saito R, Yanagida N, Ishikawa C, Uchida K, Kawaguchi T, Yanase Y, Ishiuji Y, McGrath J, and Tanaka A
- Subjects
- Humans, Mice, Animals, Oncostatin M pharmacology, Oncostatin M metabolism, Interleukin-4 metabolism, Ganglia, Spinal metabolism, Interleukin-13 metabolism, Pruritus metabolism, Interleukins genetics, Interleukins metabolism, Receptors, Interleukin metabolism, Dermatitis, Atopic metabolism, Psoriasis metabolism
- Abstract
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intermittent itchy rash. Type 2 inflammatory cytokines such as interleukin (IL)-4, IL-13, and IL-31 are strongly implicated in AD pathogenesis. Stimulation of IL-31 cognate receptors on C-fiber nerve endings is believed to activate neurons in the dorsal root ganglion (DRG), causing itch. The IL-31 receptor is a heterodimer of OSMRβ and IL31RA subunits, and OSMRβ can also bind oncostatin M (OSM), a pro-inflammatory cytokine released by monocytes/macrophages, dendritic cells, and T lymphocytes. Further, OSM expression is enhanced in the skin lesions of AD and psoriasis vulgaris patients., Objective: The current study aimed to examine the contributions of OSM to AD pathogenesis and symptom expression., Methods: The expression levels of the OSM gene ( OSM ) and various cytokine receptor genes were measured in human patient skin samples, isolated human monocytes, mouse skin samples, and mouse DRG by RT-qPCR. Itching responses to various pruritogens were measured in mice by counting scratching episodes., Results: We confirmed overexpression of OSM in skin lesions of patients with AD and psoriasis vulgaris. Monocytes isolated from the blood of healthy subjects overexpressed OSM upon stimulation with IL-4 or GM-CSF. Systemic administration of OSM suppressed IL31RA expression in the mouse DRG and IL-31-stimulated scratching behavior. In contrast, systemic administration of OSM increased the expression of IL-4- and IL-13-related receptors in the DRG., Conclusion: These results suggest that OSM is an important cytokine in the regulation of skin monocytes, promoting the actions of IL-4 and IL-13 in the DRG and suppressing the action of IL-31. It is speculated that OSM released from monocytes in skin modulates the sensitivity of DRG neurons to type 2 inflammatory cytokines and thereby the severity of AD-associated skin itch., Competing Interests: AT has received honoraria from Eli Lilly, Kaken Seiyaku, Sanofi, Taiho Pharma, Abbie, Pfizer, Kyorin Pharmaceutical, Mitsubishi-Tanabe, Torii Pharmaceutical, and Maruho as a speaker as well as research grants from Eli Lilly, Sanofi, Teijin Pharma, Taiho Pharma, Mitsubishi-Tanabe, Torii Pharmaceutical, and Maruho. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Suehiro, Numata, Saito, Yanagida, Ishikawa, Uchida, Kawaguchi, Yanase, Ishiuji, McGrath and Tanaka.)
- Published
- 2023
- Full Text
- View/download PDF
32. Ten tips for developing a more inviting syllabus.
- Author
-
Chandar S, Crum R, Pennino E, Ishikawa C, Ghosh Hajra S, and McDonald K
- Abstract
In higher education, syllabi have traditionally served as written contracts between instructors and their students, providing first-hand information about the course and expectations. Reading the syllabus may provide students with first impressions or mental images of the instructor, thereby initiating a student-instructor relationship even before any interaction has occurred. Instructors can use syllabi to directly communicate values and practices of equity and inclusion, but students can perceive indirect messages through tone and language that may support or contradict stated values. Here, we share empirically derived recommendations for improving the tone of syllabi with inviting language and stylistic features that promote relationship-building with students., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Chandar et al.)
- Published
- 2023
- Full Text
- View/download PDF
33. Inactivation of p53 provides a competitive advantage to del(5q) myelodysplastic syndrome hematopoietic stem cells during inflammation.
- Author
-
Muto T, Walker CS, Agarwal P, Vick E, Sampson A, Choi K, Niederkorn M, Ishikawa C, Hueneman K, Varney M, and Starczynowski DT
- Subjects
- Humans, Chromosome Deletion, Hematopoietic Stem Cells metabolism, Signal Transduction, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 5 metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Myelodysplastic Syndromes pathology
- Abstract
Inflammation is associated with the pathogenesis of myelodysplastic syndromes (MDS) and emerging evidence suggests that MDS hematopoietic stem and progenitor cells (HSPC) exhibit an altered response to inflammation. Deletion of chromosome 5 (del(5q)) is the most common chromosomal abnormality in MDS. Although this MDS subtype contains several haploinsufficient genes that impact innate immune signaling, the effects of inflammation on del(5q) MDS HSPC remains undefined. Utilizing a model of del(5q)-like MDS, inhibiting the IRAK1/4-TRAF6 axis improved cytopenias, suggesting that activation of innate immune pathways contributes to certain clinical features underlying the pathogenesis of low-risk MDS. However, low-grade inflammation in the del(5q)-like MDS model did not contribute to more severe disease but instead impaired the del(5q)-like HSPC as indicated by their diminished numbers, premature attrition and increased p53 expression. Del(5q)-like HSPC exposed to inflammation became less quiescent, but without affecting cell viability. Unexpectedly, the reduced cellular quiescence of del(5q) HSPC exposed to inflammation was restored by p53 deletion. These findings uncovered that inflammation confers a competitive advantage of functionally defective del(5q) HSPC upon loss of p53. Since TP53 mutations are enriched in del(5q) AML following an MDS diagnosis, increased p53 activation in del(5q) MDS HSPC due to inflammation may create a selective pressure for genetic inactivation of p53 or expansion of a pre-existing TP53-mutant clone.
- Published
- 2023
- Full Text
- View/download PDF
34. Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML.
- Author
-
Bennett J, Ishikawa C, Agarwal P, Yeung J, Sampson A, Uible E, Vick E, Bolanos LC, Hueneman K, Wunderlich M, Kolt A, Choi K, Volk A, Greis KD, Rosenbaum J, Hoyt SB, Thomas CJ, and Starczynowski DT
- Subjects
- Humans, Interleukin-1 Receptor-Associated Kinases genetics, Interleukin-1 Receptor-Associated Kinases metabolism, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Proteomics, Signal Transduction, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes genetics, Leukemia, Myeloid, Acute genetics
- Abstract
Dysregulation of innate immune signaling is a hallmark of hematologic malignancies. Recent therapeutic efforts to subvert aberrant innate immune signaling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors have achieved promising, though moderate, responses in preclinical studies and clinical trials for MDS and AML. The reasons underlying the limited responses to IRAK4 inhibitors remain unknown. In this study, we reveal that inhibiting IRAK4 in leukemic cells elicits functional complementation and compensation by its paralog, IRAK1. Using genetic approaches, we demonstrate that cotargeting IRAK1 and IRAK4 is required to suppress leukemic stem/progenitor cell (LSPC) function and induce differentiation in cell lines and patient-derived cells. Although IRAK1 and IRAK4 are presumed to function primarily downstream of the proximal adapter MyD88, we found that complementary and compensatory IRAK1 and IRAK4 dependencies in MDS/AML occur via noncanonical MyD88-independent pathways. Genomic and proteomic analyses revealed that IRAK1 and IRAK4 preserve the undifferentiated state of MDS/AML LSPCs by coordinating a network of pathways, including ones that converge on the polycomb repressive complex 2 complex and JAK-STAT signaling. To translate these findings, we implemented a structure-based design of a potent and selective dual IRAK1 and IRAK4 inhibitor KME-2780. MDS/AML cell lines and patient-derived samples showed significant suppression of LSPCs in xenograft and in vitro studies when treated with KME-2780 as compared with selective IRAK4 inhibitors. Our results provide a mechanistic basis and rationale for cotargeting IRAK1 and IRAK4 for the treatment of cancers, including MDS/AML., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
35. Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development.
- Author
-
Dean ST, Ishikawa C, Zhu X, Walulik S, Nixon T, Jordan JK, Henderson S, Wyder M, Salomonis N, Wunderlich M, Greis KD, Starczynowski DT, and Volk AG
- Subjects
- Humans, Mice, Animals, Cell Line, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Ubiquitination, Chromatin Assembly Factor-1 genetics, Chromatin Assembly Factor-1 metabolism, DNA-Binding Proteins genetics, Tumor Suppressor Proteins metabolism, Tripartite Motif Proteins genetics, Tripartite Motif Proteins metabolism, Chromatin Assembly and Disassembly, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology
- Abstract
Acute myeloid leukemia (AML) is an aggressive blood cancer that stems from the rapid expansion of immature leukemic blasts in the bone marrow. Mutations in epigenetic factors represent the largest category of genetic drivers of AML. The chromatin assembly factor CHAF1B is a master epigenetic regulator of transcription associated with self-renewal and the undifferentiated state of AML blasts. Upregulation of CHAF1B, as observed in almost all AML samples, promotes leukemic progression by repressing the transcription of differentiation factors and tumor suppressors. However, the specific factors regulated by CHAF1B and their contributions to leukemogenesis are unstudied. We analyzed RNA sequencing data from mouse MLL-AF9 leukemic cells and bone marrow aspirates, representing a diverse collection of pediatric AML samples and identified the E3 ubiquitin ligase TRIM13 as a target of CHAF1B-mediated transcriptional repression associated with leukemogenesis. We found that CHAF1B binds the promoter of TRIM13, resulting in its transcriptional repression. In turn, TRIM13 suppresses self-renewal of leukemic cells by promoting pernicious entry into the cell cycle through its nuclear localization and catalytic ubiquitination of cell cycle-promoting protein, CCNA1. Overexpression of TRIM13 initially prompted a proliferative burst in AML cells, which was followed by exhaustion, whereas loss of total TRIM13 or deletion of its catalytic domain enhanced leukemogenesis in AML cell lines and patient-derived xenografts. These data suggest that CHAF1B promotes leukemic development, in part, by repressing TRIM13 expression and that this relationship is necessary for leukemic progression., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
36. Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?
- Author
-
Nakamura T, Wada A, Yamaguchi R, Iwamoto M, Takamura K, Yanagida H, Yamaguchi T, and Ishikawa C
- Subjects
- Child, Female, Humans, Male, Coxa Magna, Femur Head diagnostic imaging, Femur Head surgery, Retrospective Studies, Treatment Outcome, Legg-Calve-Perthes Disease diagnostic imaging, Legg-Calve-Perthes Disease surgery, Osteotomy adverse effects, Osteotomy methods, Braces
- Abstract
Background: Legg-Calvé-Perthes disease (LCPD) is a childhood hip disease characterized by osteonecrosis of the femoral head. Because severe deformity of the femoral head can cause secondary osteoarthritis in adulthood, progressive collapse should be prevented in children with a necrotic epiphysis. The prognosis of patients with LCPD generally worsens as the age at disease onset increases, and the appropriate treatment for late-onset LCPD remains unclear. Based on the limited effect of nonoperative treatment using a nonweightbearing brace, flexion varus osteotomy (FVO) was introduced in 2010 as an initial treatment for late-onset LCPD in place of brace treatment, which we used in our institution before that time., Questions/purposes: We asked, (1) Which treatment, FVO or a nonweightbearing brace, is associated with a lower likelihood of progressive femoral head collapse in children whose diagnosis of LCPD was made at the age of ≥ 8 years and who were followed for a minimum of 3 years after their intervention? (2) What proportion of patients in the brace group had surgery despite the treatment, and what percentage of children in the FVO group had a second operation to remove hardware and/or additional operations?, Methods: The initial treatment was applied in 181 patients with LCPD between 1995 and 2018 in our institution. Patients whose disease onset was at ≥ 8 years old (late-onset LCPD) with complete clinical and radiologic data were considered potentially eligible. In 2010, treatment for these patients changed from brace treatment to FVO for all patients. A total of 35% (42 of 121) of patients who were treated with a nonweightbearing brace between 1995 and 2009 and 40% (24 of 60) of patients who were treated with FVO between 2010 and 2018 were eligible. Among patients treated with a brace, 21% (nine of 42 patients) were excluded because of hospital transfer (three patients), short-term follow-up (three), the period from onset to the first visit was ≥ 7 months (two), and inability to use the brace because of mental incapacity (one patient). In patients treated with FVO, 12% (three of 24 patients) were excluded (two patients with a period from onset to the first visit ≥ 7 months and one with a comorbidity and multiple-epiphyseal dysplasia). Among the remaining patients, 79% (33 of 42 patients) were classified into the brace group and 88% (21 of 24 patients) were classified into the FVO group for analyses. There were no overlapping patients at the timepoint when the treatment strategy for late-onset LCPD changed. In the FVO group, subtrochanteric osteotomy with 35° to 40° of flexion and 15° to 20° of varus was performed using a locking compression plate for pediatric use. Patient demographics, radiographic parameters, and the assessment of femoral head deformity using the Stulberg classification were compared between the two groups. There was a greater proportion of boys than girls in both groups (brace: 88% and FVO: 86%), and there were no differences in the distribution of genders between the groups (p = 0.82). The right side was more frequently treated in the brace group, but there was no difference in laterality between the groups (brace: 58% right and FVO: 62% left; p = 0.16). There was no difference between groups in the median age at disease onset (9.0 years [range 8.0 to 12.5 years] in the brace group and 9.6 years [range 8.0 to 12.4 years] in the FVO group; p = 0.26). There was no difference between the groups in the period of treatment from onset (1.7 ± 1.9 months in the brace group and 1.5 ± 1.5 months in the FVO group; p = 0.73) or the follow-up period (6.7 ± 2.1 years in the brace group and 6.2 ± 2.1 years in the FVO group; p = 0.41). The LCPD stage at the first visit was assessed using the modified Waldenström classification. The intraobserver and interobserver values of the modified Waldenström classification, evaluated using kappa statistics, were excellent (kappa value 0.89 [95% CI 0.75 to 0.97]; p < 0.01) and good (kappa value 0.65 [95% CI 0.43 to 0.87]; p < 0.01). The radiographic degree of collapse at the maximum fragmentation stage was assessed using the lateral pillar classification. The intraobserver and interobserver reliabilities of the lateral pillar classification were excellent (kappa value 0.84 [95% CI 0.73 to 0.94]; p < 0.01) and excellent (kappa value 0.83 [95% CI 0.71 to 0.94]; p < 0.01). The degree of femoral head deformity at the most recent follow-up examination was compared between the groups in terms of the Stulberg classification, in which Classes I and II were classified as good and Classes III through V were classified as poor. The intraobserver and interobserver reliabilities of the Stulberg classification were good (kappa value 0.74 [95% CI 0.55 to 0.92]; p < 0.01) and good (kappa value 0.69 [95% CI 0.50 to 0.89]; p < 0.01). The evaluators were involved in the patients' clinical care as part of the treating team., Results: Good radiographic results (Stulberg Class I or II) were obtained more frequently in the FVO group (76% [16 of 21 patients]) than in the brace group (36% [12 of 33 patients]), with an odds ratio of 5.6 (95% CI 1.7 to 18.5; p < 0.01). In the brace group, a subsequent femoral varus osteotomy was performed in 18% (six of 33) of patients with progressive collapse and hinge abduction, and implant removal surgery was performed approximately 1 year after the first procedure. This traditional varus osteotomy was occasionally performed in patients who were considered for conversion from nonoperative treatment before 2009 because FVO had not yet been introduced. In the FVO group, all patients (n = 21) had a second procedure to remove the implant at a mean of 10.5 ± 1.2 months postoperatively. Additional procedures were performed in 24% (five of 21) of patients, including a second FVO for progressive collapse (one patient), guided growth for a limb length discrepancy (one patient), and flexion valgus osteotomy for coxa vara in patients with a limb length discrepancy (three patients)., Conclusion: Our historical control study found that FVO may increase the possibility of obtaining good radiographic results (Stulberg Class I or II) compared with brace treatment for patients with late-onset LCPD, although surgical interventions after the first and second implant removal procedures may be indicated. Surgeons can consider FVO if they encounter patients with late-onset LCPD, which is a challenging condition. A larger study with long-term follow-up is needed to confirm the efficacy of FVO., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)
- Published
- 2023
- Full Text
- View/download PDF
37. Functional Alteration and Differential Expression of the Bitter Taste Receptor T2R38 in Human Paranasal Sinus in Patients with Chronic Rhinosinusitis.
- Author
-
Takemoto K, Lomude LS, Takeno S, Kawasumi T, Okamoto Y, Hamamoto T, Ishino T, Ando Y, Ishikawa C, and Ueda T
- Subjects
- Humans, Chronic Disease, Receptors, G-Protein-Coupled genetics, Taste, Nasal Polyps, Paranasal Sinuses, Rhinitis, Sinusitis metabolism
- Abstract
The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV/AVI and AVI/AVI genotype groups as compared to the PAV/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.
- Published
- 2023
- Full Text
- View/download PDF
38. Sugarcane Metabolome Compositional Stability in Pretreatment Processes for NMR Measurements.
- Author
-
Date Y, Ishikawa C, Umeda M, Tarumoto Y, Okubo M, Tamura Y, and Ono H
- Abstract
Sugarcane is essential for global sugar production and its compressed juice is a key raw material for industrial products. Sugarcane juice includes various metabolites with abundances and compositional balances influencing product qualities and functionalities. Therefore, understanding the characteristic features of the sugarcane metabolome is important. However, sugarcane compositional variability and stability, even in pretreatment processes for nuclear magnetic resonance (NMR)-based metabolomic studies, remains elusive. The objective of this study is to evaluate sugarcane juice metabolomic variability affected by centrifugation, filtration, and thermal pretreatments, as well as the time-course changes for determining optimal conditions for NMR-based metabolomic approach. The pretreatment processes left the metabolomic compositions unchanged, indicating that these pretreatments are compatible with one another and the studied metabolomes are comparable. The thermal processing provided stability to the metabolome for more than 32 h at room temperature. Based on the determined analytical conditions, we conducted an NMR-based metabolomic study to discriminate the differences in the harvest period and allowed for successfully identifying the characteristic metabolome. Our findings denote that NMR-based sugarcane metabolomics enable us to provide an opportunity to collect a massive amount of data upon collaboration between multiple researchers, resulting in the rapid construction of useful databases for both research purposes and industrial use.
- Published
- 2022
- Full Text
- View/download PDF
39. Spautin-1 inhibits mitochondrial complex I and leads to suppression of the unfolded protein response and cell survival during glucose starvation.
- Author
-
Kunimasa K, Ikeda-Ishikawa C, Tani Y, Tsukahara S, Sakurai J, Okamoto Y, Koido M, Dan S, and Tomida A
- Subjects
- Benzylamines, Cell Survival, Endoplasmic Reticulum Stress, Quinazolines pharmacology, Glucose metabolism, Unfolded Protein Response
- Abstract
The unfolded protein response (UPR) is an adaptive stress response pathway that is essential for cancer cell survival under endoplasmic reticulum stress such as during glucose starvation. In this study, we identified spautin-1, an autophagy inhibitor that suppresses ubiquitin-specific peptidase 10 (USP10) and USP13, as a novel UPR inhibitor under glucose starvation conditions. Spautin-1 prevented the induction of UPR-associated proteins, including glucose-regulated protein 78, activating transcription factor 4, and a splicing variant of x-box-binding protein-1, and showed preferential cytotoxicity in glucose-starved cancer cells. However, USP10 and USP13 silencing and treatment with other autophagy inhibitors failed to result in UPR inhibition and preferential cytotoxicity during glucose starvation. Using transcriptome and chemosensitivity-based COMPARE analyses, we identified a similarity between spautin-1 and mitochondrial complex I inhibitors and found that spautin-1 suppressed the activity of complex I extracted from isolated mitochondria. Our results indicated that spautin-1 may represent an attractive mitochondria-targeted seed compound that inhibits the UPR and cancer cell survival during glucose starvation., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
40. Effect of different contrast medium injection protocols for analysis of hepatic computed tomography perfusion in healthy dogs.
- Author
-
Amaha T, Ishigaki K, Ishikawa C, Iizuka K, Nagumo T, Tamura K, and Asano K
- Subjects
- Animals, Dogs, Liver diagnostic imaging, Perfusion veterinary, Tomography, X-Ray Computed methods, Tomography, X-Ray Computed veterinary, Contrast Media pharmacology, Iohexol pharmacology
- Abstract
Objective: To evaluate the hepatic CT perfusion (CTP) for determining the appropriate protocol for the dual-input maximum-slope model in dogs., Animals: 5 healthy dogs., Procedures: Each dog underwent CTP with different contrast medium administration protocols. Combinations of three different injected doses of iohexol (450, 600, and 750 mg/kg) and injection durations (5, 10, and 15 seconds) were used. The CT values at the aorta, portal vein, and hepatic parenchyma were measured to create a time-density curve, and CTP parameters were measured simultaneously on each hepatic lobe using a 320-row multidetector CT scanner., Results: The maximum peak enhancement at the aorta, portal vein, and hepatic parenchyma was greater with the 750-mg/kg dose than with the 450-mg/kg dose. With an injection duration of 15 seconds, the aortic enhancement peak was less, and the arrival time at the aortic enhancement peak was longer compared to that with a 5-second injection duration. The CTP parameters in the caudate process of the caudate lobe and left lateral lobe differed with different injection durations. The CTP parameters in the caudate process of the caudate lobe, left lateral lobe, and right lateral lobe differed with varying injected doses., Clinical Relevance: Our study demonstrated that rapid administration of the contrast medium was required for quantitative analysis of hepatic CTP in healthy dogs. The CTP parameters differed with respect to the contrast medium administration protocol, and it was necessary to administer the contrast medium within a fixed duration and at a fixed dose to evaluate CTP correctly.
- Published
- 2022
- Full Text
- View/download PDF
41. Student Anxiety and Engagement with Online Instruction across Two Semesters of COVID-19 Disruptions.
- Author
-
Pennino E, Ishikawa C, Ghosh Hajra S, Singh N, and McDonald K
- Abstract
The sudden shift to online learning due to the COVID-19 pandemic left many instructors wondering how to minimize anxiety while keeping students engaged in their virtual courses. In this study, we explored (i) specific online instructional tasks that caused students to experience anxiety, (ii) factors that hindered student engagement with online instruction, and (iii) changes in student anxiety and engagement between spring 2020 and fall 2020. Students enrolled in STEM classes were surveyed at the end of spring 2020 (N = 425) and fall 2020 (N = 347) semesters. Our results show that the majority of student respondents had more anxiety in fall 2020 than in spring 2020 with online learning in general, and less anonymous class activities tended to cause the greatest anxiety. Distractions from the environment and personal technologies commonly prevented engagement in both semesters, but no significant differences were observed between the spring and fall. In contrast, more students reported that health-related stress, work-related stress, and issues with technology prevented participation in fall 2020 than in spring 2020. As institutions consider expanding their online course offerings post-pandemic, these data provide valuable insight into the challenges students experienced with online instruction that can inform future pedagogical choices., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Pennino et al.)
- Published
- 2022
- Full Text
- View/download PDF
42. Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC).
- Author
-
Tanaka K, Tanabe H, Sato H, Ishikawa C, Goto M, Yanagida N, Akabane H, Yokohama S, Hasegawa K, Kitano Y, Sugiyama Y, Uehara K, Kobayashi Y, Murakami Y, Kunogi T, Sasaki T, Takahashi K, Ando K, Ueno N, Kashima S, Moriichi K, Sato K, Yuzawa S, Tanino M, Taruiishi M, Sumi Y, Mizukami Y, Fujiya M, and Okumura T
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Kaplan-Meier Estimate, Leukocyte Count methods, Lymphocytes pathology, Male, Middle Aged, Neutrophils pathology, Prognosis, Proportional Hazards Models, Prospective Studies, Stomach Neoplasms pathology, Antineoplastic Agents, Immunological therapeutic use, Lymphocytes drug effects, Neutrophils drug effects, Nivolumab therapeutic use, Stomach Neoplasms drug therapy
- Abstract
Background: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens., Patients and Methods: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated., Results: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status., Conclusions: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
43. Long-term follow-up of portal vein thrombosis in an American Cocker Spaniel with lobular dissecting hepatitis: a case report.
- Author
-
Sakamoto Y, Sato K, Ishikawa C, Kagawa Y, Nakayama T, and Sakai M
- Subjects
- Animals, Anticoagulants therapeutic use, Computed Tomography Angiography, Dog Diseases drug therapy, Dogs, Follow-Up Studies, Liver Cirrhosis veterinary, Male, Prednisolone therapeutic use, Venous Thrombosis complications, Venous Thrombosis diagnostic imaging, Dalteparin therapeutic use, Hepatitis complications, Portal Vein, Venous Thrombosis veterinary
- Abstract
Background: Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients with liver cirrhosis, portal vein thrombosis (PVT) is a common complication. However, PVT has not been reported in dogs with LDH. Herein, we describe the long-term follow-up of PVT in an American Cocker Spaniel with LDH., Case Presentation: An 8-year-old neutered male American Cocker Spaniel presented with a 1-month history of severe abdominal effusion. The dog was histopathologically diagnosed with LDH and treated with low-dose prednisolone on day 14. On day 115, computed tomography angiography (CTA) confirmed the presence of a thrombus in the portal vein. Therefore, the dog was subcutaneously administered with the anticoagulant dalteparin, and low-dose prednisolone was continued. As a follow-up for PVT, CTA examinations were performed on days 207, 515, 886, and 1168, and the dog's antithrombin and D-dimer levels were measured. Following anticoagulant therapy, the dog was confirmed to have gradually increased antithrombin activity and decreased D-dimer concentrations. In addition, although the thrombus was confirmed to be in the same area of the portal vein system by CTA, atrophy and increased CT values due to organization were observed during the follow-up period. The dog's condition remained stable without clinical signs until day 1112 when it developed hepatic encephalopathy. The dog died on day 1208. On postmortem examination, histopathologically, the liver showed marked bile duct hyperplasia and fibrosis with chronic thrombus in the portal vein., Conclusions: This case demonstrated that low-dose glucocorticoid combined with dalteparin allowed long-term follow-up of PVT in an American Cocker Spaniel with LDH., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
44. The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis.
- Author
-
Kawasumi T, Takeno S, Ishikawa C, Takahara D, Taruya T, Takemoto K, Hamamoto T, Ishino T, and Ueda T
- Subjects
- Animals, Chronic Disease, Humans, Isoenzymes, Rhinitis, Allergic metabolism, Sinusitis metabolism, Nasal Mucosa enzymology, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Paranasal Sinuses enzymology, Rhinitis, Allergic physiopathology, Sinusitis physiopathology
- Abstract
The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.
- Published
- 2021
- Full Text
- View/download PDF
45. Comparison of body composition parameters in the study of the association between body composition and pulmonary function.
- Author
-
Ishikawa C, Barbieri MA, Bettiol H, Bazo G, Ferraro AA, and Vianna EO
- Subjects
- Absorptiometry, Photon, Adult, Anthropometry, Body Mass Index, Brazil, Cross-Sectional Studies, Female, Forced Expiratory Volume physiology, Humans, Linear Models, Male, Risk Factors, Spirometry, Vital Capacity physiology, Waist Circumference physiology, Body Composition physiology, Lung physiology
- Abstract
Background: The excess adiposity, even in the absence of diseases, is responsible for a decline in pulmonary function, which is considered a predictor of mortality and a risk factor for diseases in several epidemiological studies. However, studies on the association between obesity and pulmonary function have found only few associations or inconclusive results. The aim of the study is to evaluate the association between body composition and spirometric parameters, comparing simple obesity measures such as body mass index (BMI) and waist circumference with more precise body composition measurements such as dual-energy X-ray absorptiometry (DXA) and air-displacement plethysmography (BOD POD)., Methods: This is an observational, cross-sectional study that used data from the 1978/79 Ribeirão Preto birth cohort (São Paulo, Brazil). The study included 1746 participants from the 5th follow-up of the cohort. Linear regressions were calculated to evaluate the association between BMI, waist circumference, waist-height ratio (WHtR), BOD POD- and DXA-measured fat mass percentage, and spirometric parameters FEV1, and FVC., Results: For every 1-kg/m
2 BMI increase, FVC decreased by 13 ml in males and by 6 ml in females and FEV1 decreased by 11 ml and 5 ml, respectively. Regarding body composition measurements, for a 1% increase in fat mass assessed by BOD POD, FVC decreased by 16 ml in males and by 8 ml in females and FEV1 decreased by 13 ml and 7 ml, respectively. Hence, negative associations between body measurements and FEV1 and FVC were observed in both genders, especially when using the fat mass measurement and were more expressive in men., Conclusion: The anthropometric and body composition parameters were negatively associated with the spirometric variables FVC and FEV1. We have also observed that simple measures such as waist-height ratio were sufficient to detect the association of body composition with pulmonary function reduction.- Published
- 2021
- Full Text
- View/download PDF
46. Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor.
- Author
-
Nishiya N, Oku Y, Ishikawa C, Fukuda T, Dan S, Mashima T, Ushijima M, Furukawa Y, Sasaki Y, Otsu K, Sakyo T, Abe M, Yonezawa H, Ishibashi F, Matsuura M, Tomida A, Seimiya H, Yamori T, Iwao M, and Uehara Y
- Subjects
- Acrylamides pharmacology, Aniline Compounds pharmacology, Animals, Cell Line, Tumor, Cell Proliferation drug effects, Drug Resistance, Neoplasm genetics, Drug Screening Assays, Antitumor methods, ErbB Receptors antagonists & inhibitors, ErbB Receptors genetics, ErbB Receptors metabolism, Fluoroacetates, Gene Expression, Heterocyclic Compounds, 4 or More Rings chemistry, Heterografts, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Molecular Targeted Therapy, Mollusca chemistry, Mutagenesis, Site-Directed, Mutation, Protein Kinase Inhibitors chemistry, Heterocyclic Compounds, 4 or More Rings pharmacology, Protein Kinase Inhibitors pharmacology
- Abstract
The emergence of acquired resistance is a major concern associated with molecularly targeted kinase inhibitors. The C797S mutation in the epidermal growth factor receptor (EGFR) confers resistance to osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI). We report that the derivatization of the marine alkaloid topoisomerase inhibitor lamellarin N provides a structurally new class of EGFR-TKIs. One of these, lamellarin 14, is effective against the C797S mutant EGFR. Bioinformatic analyses revealed that the derivatization transformed the topoisomerase inhibitor-like biological activity of lamellarin N into kinase inhibitor-like activity. Ba/F3 and PC-9 cells expressing the EGFR in-frame deletion within exon 19 (del ex19)/T790M/C797S triple-mutant were sensitive to lamellarin 14 in a dose range similar to the effective dose for cells expressing EGFR del ex19 or del ex19/T790M. Lamellarin 14 decreased the autophosphorylation of EGFR and the downstream signaling in the triple-mutant EGFR PC-9 cells. Furthermore, intraperitoneal administration of 10 mg/kg lamellarin 14 for 17 days suppressed tumor growth of the triple-mutant EGFR PC-9 cells in a mouse xenograft model using BALB/c nu/nu mice. Thus, lamellarin 14 serves as a novel structural backbone for an EGFR-TKI that prevents the development of cross-resistance against known drugs in this class., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2021
- Full Text
- View/download PDF
47. Cerebrospinal fluid flow on time-spatial labeling inversion pulse images before and after treatment of congenital hydrocephalus in a dog.
- Author
-
Ito D, Ishikawa C, Jeffery ND, and Kitagawa M
- Subjects
- Animals, Cerebrospinal Fluid diagnostic imaging, Dogs, Magnetic Resonance Imaging veterinary, Male, Subarachnoid Space, Dog Diseases diagnostic imaging, Dog Diseases surgery, Hydrocephalus diagnostic imaging, Hydrocephalus surgery, Hydrocephalus veterinary, Syringomyelia veterinary
- Abstract
A 3-month-old male cross-breed dog presented with signs of progressive diffuse brain disease. Noncommunicating congenital hydrocephalus concurrent with cervical syringomyelia was diagnosed on magnetic resonance images. On time-spatial labeling inversion pulse (Time-SLIP) images CSF flow through the mesencephalic aqueduct was poorly defined and there was flow into the syrinx across the craniocervical junction. After percutaneous ventricular drainage and ventriculoperitoneal shunting, CSF flow through the aqueduct was clearly detected and flow into the syrinx disappeared. In addition, CSF flow in the subarachnoid space at the pons and ventral aspect of the cervical subarachnoid space was restored. Signs of neurological dysfunction improved after ventriculoperitoneal shunting and the cerebral parenchyma was increased in thickness on 2-year follow-up computed tomography images. Patterns of CSF flow on Time-SLIP images before and after CSF drainage or ventriculoperitoneal shunting aid in clarifying disease pathogenesis and confirm effects of CSF drainage., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)
- Published
- 2021
- Full Text
- View/download PDF
48. Transcriptome analysis of sevoflurane exposure effects at the different brain regions.
- Author
-
Yamamoto H, Uchida Y, Chiba T, Kurimoto R, Matsushima T, Inotsume M, Ishikawa C, Li H, Shiga T, Muratani M, Uchida T, and Asahara H
- Subjects
- Animals, Gene Expression Profiling methods, Gene Expression Regulation genetics, Gene Ontology, Kruppel-Like Factor 4, Male, Mice, Mice, Inbred C57BL, Neurons drug effects, Transcription Factors genetics, Transcriptome genetics, Up-Regulation drug effects, Up-Regulation genetics, Brain drug effects, Gene Expression Regulation drug effects, Sevoflurane pharmacology, Transcriptome drug effects
- Abstract
Backgrounds: Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis., Methods: Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes., Results: The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes., Conclusions: Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
49. Successful management of portal vein thrombosis in a Yorkshire Terrier with protein-losing enteropathy.
- Author
-
Sakamoto Y, Ishigaki K, Ishikawa C, Nakayama T, Asano K, and Sakai M
- Subjects
- Administration, Oral, Animals, Computed Tomography Angiography veterinary, Dogs, Factor Xa Inhibitors administration & dosage, Factor Xa Inhibitors therapeutic use, Female, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Hypoalbuminemia drug therapy, Hypoalbuminemia veterinary, Portal Vein diagnostic imaging, Portal Vein pathology, Prednisolone administration & dosage, Prednisolone therapeutic use, Rivaroxaban administration & dosage, Venous Thrombosis diagnostic imaging, Venous Thrombosis drug therapy, Dog Diseases drug therapy, Protein-Losing Enteropathies veterinary, Rivaroxaban therapeutic use, Venous Thrombosis veterinary
- Abstract
Background: Portal vein thrombosis (PVT) is a rare presentation in dogs with protein-losing enteropathy (PLE). Rivaroxaban, an oral, selective, direct factor Xa inhibitor, has not been reported to be administrated for canine PVT and the effect is unclear in dogs with PLE., Case Presentation: An 11-year-old Yorkshire Terrier presented with moderate ascites. The dog had severe hypoalbuminemia (1.2 g/dL), and a portal vein thrombus was confirmed on computed tomographic angiography (CTA). On endoscopic examination, it became apparent that the hypoalbuminemia was caused by PLE, which was consequent of lymphatic dilation and lymphoplasmacytic enteritis. Therefore, the dog was initially treated with oral administrations of spironolactone and clopidogrel, with dietary fat restriction. However, a follow-up CTA showed no changes in the ascites, thrombus, and portal vein to aorta (PV/Ao) ratio. Therefore, the dog was additionally prescribed rivaroxaban and low-dose prednisolone for the portal vein thrombus and hypoalbuminemia due to lymphoplasmacytic enteritis, respectively. Following the treatment, the PV/Ao ratio decreased because of a decrease in the thrombus and the ascites disappeared completely with an elevation of albumin concentration (1.9 g/dL)., Conclusions: This case report demonstrated that oral administration of rivaroxaban combined with low-dose glucocorticoid was effective management for PVT in a dog with PLE.
- Published
- 2020
- Full Text
- View/download PDF
50. Diagnostic utility of computed tomographic angiography in dogs with portal vein thrombosis.
- Author
-
Sato K, Sakamoto Y, Sakai M, Ishikawa C, Nakazawa M, Cheng CJ, Watari T, and Nakayama T
- Subjects
- Angiography veterinary, Animals, Computed Tomography Angiography veterinary, Dogs, Portal Vein diagnostic imaging, Retrospective Studies, Tomography, X-Ray Computed veterinary, Dog Diseases diagnostic imaging, Thrombosis veterinary
- Abstract
Computed tomographic (CT) angiography, the gold standard for diagnosing portal vein thrombosis (PVT) in humans, is poorly documented in dogs. Therefore, we retrospectively reviewed dogs with PVT diagnosed by CT angiography. Medical records of 13 client-owned dogs diagnosed with PVT by CT angiography were reviewed. All dogs had chronic PVT, and the most frequent clinical sign was vomiting (5/13), with pancreatitis the most frequent concurrent disease (6/13). All dogs tested for plasma D-dimer concentration (12/12) revealed elevated levels. On CT angiography, a thrombus was detected as a non-contrast enhancement structure in the portal vessel of 13 dogs. There was no evidence of complete obstruction of the portal vein in any of the dogs. The median luminal filling of the portal vein was 60.4%. The thrombus extension was variable among dogs, with a median of 34.9 mm. CT angiography identified the thrombus in the main portal vein of 12/13 dogs and multiple thrombus formation other than the main portal vein in 9/13 dogs. CT angiography provided specific information such as detecting the presence, location, and number of PVT in dogs. Therefore, CT angiography might be useful for the diagnosis and follow-up evaluation of PVT in dogs.
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.