The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 266, Issue 4
August
Displaying 1-10 of 10 articles from this issue
Regular Contribution
  • Selcuk Coskun, Serkan Demircan, Gul Pamukcu Gunaydin, Karabekir Ercan
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 305-309
    Published: 2025
    Released on J-STAGE: August 08, 2025
    Advance online publication: February 13, 2025
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    Sometimes, non-contrast computed tomography (NCCT) is the only neuroimaging technique available due to the disadvantages of magnetic resonance imaging (MRI) (e.g., MRI is not suitable for patients with a cardiac pacemaker, hemodynamically unstable patients etc.). This study aims to examine the use of Hounsfield Unit (HU) measurement comparison of symmetrical anatomical regions in opposite hemispheres of the brain for the early diagnosis of acute ischemic stroke patients. Eighty-one ischemic stroke patients were included in this retrospective study. Infarct areas were defined in diffusion-weighted magnetic resonance imaging (DWMRI) as hyperintense areas. The same anatomical regions were then identified in previously performed computed tomography, and the density of these areas in HUs was measured. Symmetrical anatomical regions were found in the opposite hemisphere, and HU measurements of these areas were obtained. The means of infarct area HU measurements and normal area HU measurements were compared between groups. The infarct area HU measurements (IAHUm) were significantly lower than the symmetrical normal area HU measurements (NAHUm) (p < 0.001) in all patient groups. The ratio of infarct to normal area HU measurements (rHU) showed remarkable consistency across groups (0.75, 0.77, 0.68). Our findings suggest that comparing HU measurements is an effective means of early diagnosis for ischemic stroke. We propose that this technique may be useful for patients when DWMRI is not available or not suitable. We further suggest that this technique can be used more accurately if the calculations are done automatically by computer software.

  • Naoki Tokunaga, Hisato Shima, Takuya Okamoto, Masato Maekawa, Jun Mina ...
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 311-317
    Published: 2025
    Released on J-STAGE: July 30, 2025
    Advance online publication: January 16, 2025
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    Serum butyrylcholinesterase (BChE) levels are positively correlated with serum albumin levels and are influenced by inflammation. Heterozygous BChE deficiency in patients on dialysis may be overlooked as malnutrition owing to dialysis-associated low BChE and albumin levels. In this study, we aimed to clarify a method for identifying low BChE levels due to hereditary causes. This single-center, retrospective, observational study included 1,104 patients undergoing dialysis and 1,716 patients not undergoing dialysis. Patients on dialysis with available data of high-sensitivity C-reactive protein (hsCRP) levels were divided into three groups according to the hsCRP level: low (< 1 mg/L), average (1-3 mg/L), and high (> 3 mg/L), and the association of serum hsCRP level with BChE and albumin levels was investigated. We compared intercept values (y value at x = 0) of the regression formula obtained from repeated measurements between patients on dialysis and those with a known hereditary heterozygous BChE deficiency. Serum BChE and albumin levels in patients on dialysis were significantly lower, and a positive correlation was observed. The hsCRP level and the BChE and albumin levels were negatively correlated. BChE and albumin levels were highest in the low hsCRP group and lowest in the high hsCRP group, and a significant positive correlation was observed in all groups. The intercept values of the regression formula obtained from repeated measurements of BChE and albumin levels in patients on dialysis and a patient with hereditary heterozygous BChE deficiency were 0.383 and ­­–102.730, respectively, which may be useful in distinguishing hereditary causes.

Case
  • Hideyuki Hawaka, Katsuaki Toyoshima, Tomoko Saito, Tomoyuki Shimokaze, ...
    Article type: Case
    2025Volume 266Issue 4 Pages 319-326
    Published: 2025
    Released on J-STAGE: August 08, 2025
    Advance online publication: March 06, 2025
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    We herein present a case of simple aortic coarctation (CoA) after ductus arteriosus ligation, in which the combination of a phosphodiesterase-3 (PDE3) inhibitor with liposomal prostaglandin E1 (lipoPGE1) improved the pressure gradient between the upper and lower limbs and enhanced left ventricular function. A female infant was born at 29 weeks 1 day of gestation as the smaller twin in a monochorionic diamniotic pregnancy, with a birth weight of 744 g (–3.0 SD). She was diagnosed with simple CoA at 2 days of age and treated with lipoPGE1. However, because of progressive congestive heart failure, patent ductus arteriosus ligation was performed at 9 days of age. By 21 days of age, the pressure gradient between her upper and lower limbs worsened to 55 mmHg despite continued lipoPGE1 treatment. At that point, the PDE3 inhibitor olprinone was introduced in combination with lipoPGE1. After starting the combination therapy, the pressure gradient decreased to 24 mmHg while the blood pressure in the lower extremities remained similar, and the left ventricular function improved. The PDE3 inhibitor may have contributed to improving the stenosis of the CoA site. Further studies are needed to clarify the efficacy of this treatment.

  • Tomohiro Yoshida, Keisuke Nishimura, Kei Hirose, Hiroyuki Murabe
    Article type: Case
    2025Volume 266Issue 4 Pages 327-334
    Published: 2025
    Released on J-STAGE: August 07, 2025
    Advance online publication: January 30, 2025
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    Neuromyelitis optica spectrum disorder is an inflammatory disease of central nervous system. Autoantibodies against aquaporin 4 (anti-AQP4-ab) are often present in neuromyelitis optica spectrum disorder and have pathogenic effects on central nervous system. Aquaporin 4 is also expressed in peripheral organs, and some cases of anti-AQP4-ab-positive neuromyelitis optica spectrum disorder with peripheral organ involvement have recently been reported. Here, we report a unique case of anti-AQP4-ab-positive neuromyelitis optica spectrum disorder. A 58-year-old man was admitted with fever, interstitial pneumonia, and markedly increased serum-creatine kinase levels (up to 300,200 U/L). Skeletal muscle biopsy revealed rhabdomyolysis. Collagen and infectious diseases were excluded; therefore, adverse effects of prescription drugs were initially suspected. Clinical symptoms improved with steroid administration and discontinuation of all previously prescribed medications. However, bilateral vision loss, bilateral lower-limb muscle weakness, and bilateral lower-limb sensory disturbances appeared later, and fever and increased serum-creatine kinase levels recurred. The patient was diagnosed with neuromyelitis optica spectrum disorder with peripheral organ (lung and skeletal muscles) involvement based on magnetic resonance imaging findings and serum anti-AQP4-ab positivity. Our case demonstrates that interstitial pneumonia and rhabdomyolysis can be the initial symptoms and indicators of the relapse of anti-AQP4-ab-positive neuromyelitis optica spectrum disorder, and skeletal muscle involvement can lead to markedly elevated creatine kinase levels.

Regular Contribution
  • Shigeyuki Murono, Sayaka Yagi-Nakanishi, Kazuhira Endo, Satoru Kondo, ...
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 335-342
    Published: 2025
    Released on J-STAGE: August 08, 2025
    Advance online publication: December 12, 2024
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    Allergic rhinitis, especially Japanese cedar pollinosis, is considered a national affliction in Japan. The present exploratory study focused on the AllergoOncologic aspect of head and neck cancer (HNC) from the perspective of serum allergen-specific IgE against Japanese cedar pollen (JCP) for the first time. Serum JCP-specific IgE was measured in seventy-five HNC patients, including the oropharynx, hypopharynx, and larynx, and seventeen nasopharyngeal cancer (NPC) patients as well as forty-two patients with non-allergic benign disease (nABD). The JCP-specific IgE-positive rate was significantly lower in HNC than nABD (p = 0.037). Similarly, there was a clear trend toward a lower JCP-specific IgE score in HNC than nABD (p = 0.069). Further analyses excluding subjects in their 70s or older also showed that the JCP-specific IgE-positive rate was significantly lower in HNC than nABD (p = 0.022). In addition, The JCP-specific IgE score was significantly lower in HNC than nABD (p = 0.045). A lower serum JCP-specific IgE-positive rate in patients with HNC compared with nABD was demonstrated for the first time. An inverse correlation between HNC and Japanese cedar pollinosis was suggested from the perspective of allergen-specific IgE.

  • Hong Qu, Bingbing Song, Yang Lin, Jiao Liu
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 343-351
    Published: 2025
    Released on J-STAGE: August 21, 2025
    Advance online publication: February 27, 2025
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    Offline cognitive-behavioral stress caring program (CBSC) modifies maladaptive cognition and improves management stress skills, which relieves mental disorders in some cancer patients; however, it is limited by space and time. This study compared the effect of online and offline CBSC on mental health, spiritual well-being, fatigue, and patient satisfaction in prostate cancer survivors after prostatectomy. Totally, 147 prostate cancer survivors after prostatectomy were divided into offline (n = 89) and online (n = 58) CBSC groups. CBSC included stress management, relaxation, disease-relevant education, and weekly homework. Selection bias was adjusted by matching patients in both groups (1:1) using propensity scores (n = 58 in both groups after adjustment). Hospital Anxiety and Depression Scale (HADS)-anxiety, HADS-depression, Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale (FACIT-SP), the brief fatigue inventory-China (BFI-C), and patient satisfaction score (PSS) were evaluated. ‘Improvement’ was defined as positive improvement values in indexes after a 10-week CBSC. Before and after adjustment, HADS-anxiety, HADS-depression, FACIT-SP, BFI-severity, and BFI-interference scores were improved at week 10 vs. baseline in the online or offline CBSC group. However, these scores did not vary at baseline or week 10 between groups. The improvement of HADS-anxiety, HADS-depression, and FACIT-SP scores was smaller in online CBSC group than in offline CBSC group. The improvement of BFI-severity and BFI-interference scores were non-differential between groups. PSS scores were reduced in online CBSC group vs. offline CBSC group. Overall, online CBSC alleviates mental disorders, elevates satisfaction, and relieves fatigue in prostate cancer survivors after prostatectomy, but its overall effect is less than offline CBSC.

  • Shasha Zhang, Meiai Xu, Xuefeng Shen, Sicong Jiang, Xianming He, Juyin ...
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 353-360
    Published: 2025
    Released on J-STAGE: August 21, 2025
    Advance online publication: November 07, 2024
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    Nasopharyngeal carcinoma (NPC) is a serious malignancy occurring in nasopharynx with high incidence, which is caused by excessive proliferation of nasopharyngeal cells. It has been reported that both microRNA (miR)-616-5p and glycogen synthase kinase 3β (GSK3β) are involved in multiple biological processes in various cancer cells and there is a targeting relationship between them. However, their roles in NPC remain undiscovered. This study was to investigate the prognosis and regulatory role of miR-616-5p/ GSK3β in NPC. 136 patients with NPC were enrolled and provided tissue samples. The NPC cell line SUNE-1 was used to explore the effect of miR-616-5p on NPC. Cell transfection was used to regulate gene expression and the expression levels of miR-616-5p and GSK3β were confirmed by qRT-PCR. Results confirmed that miR-616-5p was increased in both NPC tissues of patients and NPC cell lines. Further Kaplan-Meier assay showed that increased miR-616-5p was related to the poor prognosis of NPC patients. Subsequent assessment on cellular biological behavior demonstrated that up-regulated miR-616-5p facilitated cell proliferation, migration and invasion while it suppressed cell apoptosis. In addition, GSK3β was identified as a potential downstream target of miR-616-5p by dual-luciferase system. In conclusion, up-regulated miR-616-5p may promote the progression of NPC via targeting GSK3β.

  • Natsumi Joko, Takako Kikkawa, Takayoshi Inoue, Noriko Osumi
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 361-369
    Published: 2025
    Released on J-STAGE: August 22, 2025
    Advance online publication: June 05, 2025
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    Sex differences are increasingly recognized as critical factors influencing the onset and manifestation of various neurodevelopmental disorders, including autism spectrum disorder (ASD). Among ASD-associated genes, Pax6, which encodes a transcription factor, has been implicated in sex-dependent phenotypes when mutated. The anterior commissure (AC), a major commissural pathway involved in higher cognitive and social functions, exhibits structural abnormalities both in individuals with ASD and in those carrying Pax6 mutations. Anatomically, the AC consists of two principal fiber bundles: the anterior limb (aAC), connecting the olfactory bulbs and anterior olfactory nucleus, and the posterior limb (pAC), connecting the piriform cortex and amygdaloid regions, both converging at the midline. In this study, we investigated sex-specific structural abnormalities of the AC in Pax6 mutant mice. Analysis of horizontal and sagittal AC sections revealed that Pax6 haploinsufficiency in mice induces abnormal de-fasciculation in the aAC and aberrant intermingling of aAC and pAC fibers at the midline. Notably, Pax6 mutant females exhibited more diverse phenotypes. These females showed a pronounced reduction in overall AC size and disruptions in pAC shape regularity, likely due to a more severe disruption of the boundary between the aAC and pAC axon bundles. These sex-dependent alterations in AC morphology may contribute to the sexually dimorphic phenotypes observed in various neurodevelopmental disorders, including autism spectrum disorder.

  • Junwei Xu, Xingxing Wu, Yali Zhang, Ying Jin, Caijiao Wang, Chunchun X ...
    Article type: Regular Contribution
    2025Volume 266Issue 4 Pages 371-379
    Published: 2025
    Released on J-STAGE: August 22, 2025
    Advance online publication: November 07, 2024
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    Supplementary material

    Carotid artery stenosis (CAS) is mostly caused by carotid atherosclerotic plaque, leading to various cardiovascular and cerebrovascular diseases that seriously threaten human lives. This study aims to explore the roles of LINC01094 and hsa-miR-4758-5p in CAS pathogenesis and provide theoretical support for its prediction and treatment. RT-qPCR was used to detect the levels of LINC01094 and hsa-miR-4758-5p. SPSS software was utilized to construct the Receiver Operating Characteristic (ROC) curves for diagnosingCAS using LINC01094 and hsa-miR-4758-5p. The interaction between LINC01094 and hsa-miR-4758-5p was tested using a dual-luciferase reporter gene assay. CCK-8 assay and flow cytometry were employed to assess cell activity and apoptotic cell ratio, respectively. The Western Blotting assay detected the expression of BAK, BCL-2, and ICAM-1. ELISA, lipid peroxidation (MDA), and reactive oxygen species (ROS) kits measured the levels of inflammatory factors (IL-6 and TNF-α), MDA, and ROS, respectively. LINC01094 expressed highly, and hsa-miR-4758-5p expressed lowly in CAS. The combination of LINC01094 and hsa-miR-4758-5p showed higher accuracy in diagnosing CAS compared to either factor alone. The hsa-miR-4758-5p mimic significantly reduced the luciferase activity of HCAECs and THP-1 cells transfected with wt-LINC01094 vectors. LINC01094 overexpression suppressed the level of hsa-miR-4758-5p. The hsa-miR-4758-5p mimic reversed cell damage induced by ox-LDL or LINC01094 overexpression. LINC01094 and hsa-miR-4758-5p had good diagnostic value in CAS. Mechanistically, LINC01094 mediated ox-LDL-induced damage of HCAECs and THP-1 cells by negatively regulating hsa-miR-4758-5p.

Case
  • Kosuke Yamaka, Daiki Aomura, Makoto Harada, Takayuki Nimura, Koji Hash ...
    Article type: Case
    2025Volume 266Issue 4 Pages 381-386
    Published: 2025
    Released on J-STAGE: August 27, 2025
    Advance online publication: October 24, 2024
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    Despite receiving immunosuppressive therapy, a 37-year-old woman with lupus nephritis experienced refractory nephrotic syndrome and severe kidney dysfunction that necessitated peritoneal dialysis. Thereafter, immunosuppressants were tapered because her lupus symptoms improved. Two weeks after prednisolone termination, she was hospitalized because of acute abdominal pain. A physical examination revealed upper abdominal tenderness. Her dialysate was cloudy and comprised an elevated neutrophil count. A coronavirus disease 2019 test yielded positive results. Infectious peritonitis was suspected, coronavirus disease 2019 was diagnosed, and antibiotic and steroid therapies were initiated. The patient’s symptoms improved rapidly, and steroid therapy was discontinued on day 9. On day 10, she experienced abdominal pain and exhibited an elevated monocyte-predominant dialysate cell count despite antibiotic treatment. The dialysate culture results were negative. Lupus peritonitis was suspected because of her slightly elevated dsDNA antibodies and changes in the dialysate cell fraction. Prednisolone was resumed on day 12. Her symptoms improved immediately, and she was discharged on day 30 without complications. This case highlights unique autoimmune activation by coronavirus disease 2019 (COVID-19) that resulted in unexpected pathological shifts and challenging diagnoses. Clinicians should consider various causes of immune flare-ups in patients with COVID-19 and autoimmune conditions.

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