Publications by authors named "Yukiko Ishikawa"

Body rocking can either induce sleep or arousal. That is, the vestibular sense influences sleep-wake states. Neuronal interactions between sleep-wake systems and vestibular systems, however, remain unclear.

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  • Low-dose radiation has significant effects on undifferentiated cells but its specific impacts on developing retinal cells are not fully understood.
  • This study examined human retinal cells created from induced pluripotent stem cells (iPSCs) after exposure to low-dose radiation, discovering that different radiation levels (30 vs. 180 mGy) influenced gene expression and cellular development distinctly.
  • Results indicated that while 30 mGy promoted the growth of essential eye development factors and certain retinal cells, 180 mGy led to decreased levels and suggested a dedifferentiation and neural development response, indicating that developing retinal cells adapt through complex biological mechanisms under stress conditions.
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Idiopathic hypersomnia (IH) is a chronic neurologic disorder with unknown mechanisms that result in long night-time sleep, daytime sleepiness, long non-refreshing naps, and difficult awakening presenting as sleep drunkenness. IH patients are typically diagnosed by shorter sleep latency on multiple sleep latency test (MSLT) along with long sleep time. Only symptomatic drug treatments are currently available for IH and no animal model to study it.

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Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia.

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Orexins are a family of neuropeptides that regulate various physiological events, such as sleep/wakefulness as well as emotional and feeding behavior, and that act on two G-protein-coupled receptors, i.e., orexin 1 (OXR) and orexin 2 receptors (OXR).

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The risk of cardiovascular diseases (CVD) by chronic kidney disease (CKD) stratified by age and sex has not been examined in detail in rural Japanese populations. Therefore, we herein investigated the long-term risk of CVD by CKD and performed an age- and sex-stratified risk analysis. We examined 5163 subjects who underwent health screening between 1992 and 1995 with calculated eGFR and follow-up information on CVD events.

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  • An 82-year-old man was found to have Behçet's-like disease and myelodysplastic syndrome (MDS), which is a blood disorder.
  • He experienced joint pain and a fever that happened every two weeks for three months, and tests showed problems in his colon and bone marrow.
  • The doctors tried different treatments, but only one medicine, canakinumab, helped a little with his fever, highlighting the need to check for MDS in older patients with similar symptoms.
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A novel series of 1,3,5‑trioxazatriquinane with multiple effective residues (TriMER) derivatives with amino-methylene side chains was designed and synthesized based on the docking-simulation results between orexin receptors (OXRs) and TriMER-type OXR antagonists. In vitro screening against orexin receptors identified six TriMER derivatives with a cis side-chain configuration, and, among these, 20d and 28d showed full agonist activity against OXR at a concentration of 10 µM. To determine the absolute stereochemistry of these hit compounds, we also conducted the first asymmetric synthesis of a 1,3,5‑trioxazatriquinane skeleton using a Katsuki-Sharpless asymmetric epoxidation as the key reaction and obtained a set of the individual stereoisomers.

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Acquired loss of hypothalamic orexin (hypocretin)-producing neurons causes the chronic sleep disorder narcolepsy-cataplexy. Orexin replacement therapy using orexin receptor agonists is expected as a mechanistic treatment for narcolepsy. Orexins act on two receptor subtypes, OX1R and OX2R, the latter being more strongly implicated in sleep/wake regulation.

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Structurally diverse small compounds are utilized to obtain hit compounds that have suitable pharmacophores in appropriate three-dimensional conformations for the target drug receptors. We have focused on the 1,3,5-trioxazatriquinane skeleton, which has a rigid bowl-like structure enabling the diverse orientation of side chain units, leading to a novel small-scale focused library based on the skeleton. In the library screening for the orexin receptor, some of the compounds showed orexin receptor antagonistic activity with a high hit rate of 7%.

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  • Recent findings suggest the cerebellum, traditionally known for motor control, also influences memory, cognition, addiction, and social behavior.
  • A study using conditional knockout mice lacking the cerebellar cortex found no major differences in sleep-wake patterns compared to control mice, suggesting the cerebellum may not significantly regulate sleep.
  • However, the cKO mice displayed reduced slow wave activity and increased delta power in response to sleep deprivation, indicating the cerebellum might still play a role in slow wave generation during sleep.
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Background: Lymphomas, including Hodgkin lymphoma and non-Hodgkin lymphoma, are one of the differentials for peripheral lymphadenopathy and are difficult to diagnose clinically. Biopsy is essential for diagnosing lymphoma, although it is invasive. Non-invasive methods are required to identify patients with suspected lymphoma who should undergo a biopsy.

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A novel series of 1-amino-tetralin derivatives were designed and synthesized based on the putative binding mode of the naphthalene-type orexin receptor agonist 5 and their agonist activities against orexin receptors were evaluated. The introduction of N-methyl-(3-methoxyphenyl)acetamide unit onto the 1-amino-tetralin skeleton remarkably enhanced the potency of the agonist. The asymmetric synthesis of 6 revealed that (-)-6 having a (S)-1-amino-tetralin skeleton showed a OXR selective agonist activity (EC = 2.

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The five-membered D-ring nalfurafine (d-nor-nalfurafine) derivatives with a 16-sulfonamide group were synthesized. Conversion of the 16-cyclopropylmethyl group to the 16-benzenesulfonamide group in the d-nor-nalfurafine derivatives drastically improved the orexin 1 receptor (OXR) antagonist activities. The intramolecular hydrogen bond between the 14-hydroxy and the 16-sulfonamide groups may play an important role in increasing the probability that the 6-amide group would be located at the lower side of the C-ring, leading to an active conformation for OXR.

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A novel series of naphthalene derivatives were designed and synthesized based on the strategy focusing on the restriction of the flexible bond rotation of OXR selective agonist YNT-185 (1) and their agonist activities against orexin receptors were evaluated. The 1,7-naphthalene derivatives showed superior agonist activity than 2,7-naphthalene derivatives, suggesting that the bent form of 1 would be favorable for the agonist activity. The conformational analysis of 1,7-naphthalene derivatives indicated that the twisting of the amide unit out from the naphthalene plane is important for the enhancement of activity.

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To investigate the contribution of hydrogen bonding between the 14-hydroxy group and the 6-amide chain on the binding affinity of nalfurafine toward KOR and OXR, we prepared the 14-H and 14-dehydrated nalfurafine and their five-membered D-ring nalfurafine (D-nor-nalfurafine) derivatives. The 14-H and 14-dehydrated nalfurafine derivatives showed almost the same affinity for KOR as nalfurafine and more potent affinity for OXR. On the other hand, 14-H and 14-dehydrated D-nor-nalfurafine derivatives showed weak affinity for KOR and almost no affinity for OXR.

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Guillain-Barré syndrome (GBS) usually has a good prognosis; however, patients may develop sequelae without prompt treatment. We herein describe an 81-year-old woman who developed acute-onset excruciating thigh pain and weakness in her lower extremities after spinal surgery. We diagnosed acute inflammatory demyelinating polyradiculoneuropathy by a nerve conduction study, which showed findings of demyelination without cerebrospinal fluid analysis because of a spinal prosthesis.

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Background: Cervical lymphadenopathy is commonly seen in general practice, and its etiology is diverse. Establishing the diagnostic strategy for lymphadenopathy would be desirable to avoid overlooking neoplasms or other critical conditions. This study aims to identify the useful laboratory parameters for cervical lymphadenopathy that require clinical observation or intervention.

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Contrast-enhanced computed tomography angiography reveals "railroad track-like" calcifications bilaterally from the femoral to the popliteal arteries.

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The D-nor-nalfurafine derivatives, which were synthesized by contraction of the six-membered D-ring in nalfurafine (1), had no affinity for orexin 1 receptors (OXRs). The 17N-lone electron pair in 1 oriented toward the axial direction, while that of D-nor-derivatives was directed in the equatorial configuration. The axial lone electron pair can form a hydrogen bond with the 14-hydroxy group, which could push the 6-amide side chain toward the downward direction with respect to the C-ring.

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Cortical neurons fire intermittently and synchronously during non-rapid eye movement sleep (NREMS), in which active and silent periods are referred to as ON and OFF periods, respectively. Neuronal firing rates during ON periods (NREMS-ON-activity) are similar to those of wakefulness (W-activity), raising the possibility that NREMS-ON neuronal-activity is fragmented W-activity. To test this, we investigated the patterning and organization of cortical spike trains and of spike ensembles in neuronal networks using extracellular recordings in mice.

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We investigated the effectiveness of epinephrine auto-injector (EpiPen®) skill training for Yogo teachers in the community medicine. The auto-injector skill training might be effective for establishing a caring system for anaphylaxis at schools in the context of community medicine.

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The morphinan-type orexin 1 receptor (OXR) antagonists such as YNT-707 (2) and YNT-1310 (3) show potent and extremely high selective antagonistic activity against OXR. In the course of our studies of the essential structure of 2, we identified new scaffolds by simplification of the morphinan skeleton. However, the new chemical entities carrying the D-ring removed scaffold showed insufficient activity.

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Bovine spongiform encephalopathy (BSE) prion is more resistant to heat inactivation compared to other prions, but the effect of heat inactivation has been reported to differ depending on the BSE-contaminated tissue state or heating type. We aimed to evaluate the secure level of inactivation of original BSE transmissibility by dry-heating. Cattle tissues affected with BSE were subjected to dry-heat treatment for 20 min at various temperatures ranging from 150 to 1000 °C.

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The orexin 1 receptor (OXR) antagonists carrying a morphinan skeleton such as YNT-707 (2) and YNT-1310 (3) showed potent and extremely high selective antagonistic activity against OXR. In the course of our study of the essential structure of YNT-707 for high binding affinity against OXR, we prepared derivatives of 2 without the D- and 4,5-epoxy rings to clarify the roles of these structural determinants toward OXR antagonistic activity. The D- and 4,5-epoxy rings played important roles for the active orientation of the 17-sulfonamide and 6-amide side chains.

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