Publications by authors named "Hikaru Nakamura"

31 Publications

Moyamoya Disease Associated with Graves' Disease and Down Syndrome: A Case Report and Literature Review.

J Stroke Cerebrovasc Dis 2021 Jan 30;30(1):105414. Epub 2020 Oct 30.

Department of Neurosurgery, Nagasaki Prefecture Shimabara Hospital, 7895 Shimokawasiri, Shimabara, Nagasaki 855-0816, Japan.

Background: Moyamoya vessels are cerebral vasculopathies characterized by net-like collateral vessel formation at the cerebral basal area and stenosis of the terminal internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery. A diagnosis of Moyamoya disease depends on the bilateral presence of Moyamoya vessels. Moyamoya disease associated with Graves' disease has rarely been reported to be a cause of ischemic events due to hyperthyroidism. However, there are extremely rare cases of Moyamoya disease with concurrent Graves' disease and Down syndrome. We aimed to report such a case, and to compare these cases' clinical features, pathogenesis, and treatment effects to those of the cases of concurrent Moyamoya disease and Graves' disease alone.

Methods: We performed an English literature search using the PubMed database and the keywords Moyamoya, quasi-Moyamoya, Graves' disease, thyrotoxicosis, Down syndrome, and trisomy 21.

Results: Only five cases of Moyamoya disease with Graves' disease and Down syndrome have been reported, including our own. Four patients were female (80%), and all underwent antithyroid therapy and experienced ischemic episodes, including transient ischemic attacks. At the time of their vascular accident, two patients were in a thyrotoxic state; only our patient was in a euthyroid state. The mean age was 15.6 years (standard deviation: 6.1), which was younger than the mean age of 31.4 years (standard deviation: 13) in patients with Moyamoya disease and Graves' disease alone. Down syndrome is commonly associated with abnormal vascular networks due to increased endostatin concentrations or immunological abnormalities such as those that occur in Graves' disease. Graves' disease accelerates the progression of Moyamoya disease and ischemic attacks due to atherosclerosis, enhances sympathetic nervous system activity and immunological changes. As compared to Moyamoya disease patients, patients with concurrent Graves' disease only and Moyamoya disease patients with concurrent Graves' disease and Down syndrome may experience accelerated disease progression or more frequent ischemic attacks.

Conclusion: Early imaging follow-ups and strict control of thyroid function are necessary in such cases; if ischemic attacks have already occurred, revascularization surgery may be effective.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105414DOI Listing
January 2021

[Endovascular Treatment of a Ruptured Aneurysm of the Right Vertebral Artery with an Aberrant Right Subclavian Artery].

No Shinkei Geka 2020 Mar;48(3):223-229

National Hospital Organization Nagasaki Medical Center.

We report a rare case of the endovascular treatment of a ruptured aneurysm of the right vertebral artery with an aberrant right subclavian artery(ARSA). A 60-year-old woman was urgently admitted because of consciousness disturbance. Brain CT showed subarachnoid hemorrhage, and CT angiography showed a right vertebral ruptured aneurysm. Endovascular treatment of the aneurysm was performed via a transfemoral approach. During the endovascular treatment, the right subclavian artery was found to diverge from the descending aorta on the periphery of the left subclavian artery. An ARSA was detected, and the right vertebral artery(VA)originated from the ARSA. The guiding catheter was passed through the right VA via an ARSA, and the aneurysm was completely embolized. The patient was transferred to another hospital on day 44 without any motor weakness. To our knowledge, this is the first case of an ARSA with a ruptured aneurysm in the right VA for which endovascular treatment was successfully performed via the ARSA. In patients with an ARSA or aberrant left subclavian artery, the artery could merge with Kommerell's diverticulum(KD)at its origin and be histologically fragile. Thus, in patients with an ARSA, attention should be paid to catheterization to avoid injuring the KD. CT angiography of the aortic arch might be considered before endovascular treatment.
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http://dx.doi.org/10.11477/mf.1436204166DOI Listing
March 2020

[Reversible Cerebral Vasoconstriction Syndrome with Cortical Subarachnoid Hemorrhage due to Acute Cortical Infarction Beneath the Sulcus:A Case Report].

No Shinkei Geka 2019 Oct;47(10):1073-1079

Residency Program, Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center.

We report a rare case of reversible cerebral vasoconstriction syndrome(RCVS)with cortical subarachnoid hemorrhage(cSAH)associated with a fresh cortical infarction beneath the sulcus with thick cSAH. A 34-year-old woman presented with history of thunderclap headache. She was transferred to our hospital for further examination of a cSAH in the left frontal lobe. Results of the cerebrospinal fluid examination were unremarkable, but three-dimensional rotational angiography revealed multiple instances of narrowing of the cortical branches of the anterior and middle cerebral arteries, suggesting the diagnosis of RCVS. Diffusion weighted imaging(DWI)demonstrated a small cortical area with high-signal intensity around the sulcus , where a thick cSAH clot was observed. This cortical lesion appeared as low-signal intensity on the apparent diffusion coefficient maps, and the follow-up T2-weighted images(obtained 3 months after onset)demonstrated a residual lesion that was smaller than the initial DWI abnormality with high-signal intensity;thus indicating the presence of a coincident fresh cortical infarction. The position of the infarct next to the thickest portion of cSAH suggested that it was the bleeding source of the cSAH. Ten days after onset, the cerebral blood flow and volume in the cortex around the cSAH increased as compared to the same area on the contralateral side. These findings suggested that at least one of the bleeding mechanisms of the cSAH was related to the hemorrhagic infarction or subpial hemorrhage resulting from the "ischemia-reperfusion injury" due to the acute disturbance of the pial vessel microcirculation with subsequent rapid resolution of the blood flow during the early phases of RCVS. These dynamics could not be demonstrated with contemporary angiographic imaging.
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http://dx.doi.org/10.11477/mf.1436204076DOI Listing
October 2019

[A Rare Case of an Unruptured Fusiform Aneurysm Arising from the Lateral Limb of the Fenestration of the Anterior Medullary Segment of the Posterior Inferior Cerebellar Artery].

No Shinkei Geka 2019 Sep;47(9):991-997

Residency Program, Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center.

We report an extremely rare case of fenestration of the posterior inferior cerebellar artery(PICA)with an aneurysm at the fenestrated portion. A 60-year-old man with a medical history of hemophilia was referred to our hospital for further examination of unruptured aneurysms at the left PICA and vertebral artery(VA)that were incidentally discovered by computed tomography angiography 5 years ago during an examination of spontaneous intracerebral hemorrhage. A 3D-rotational angiography revealed a fenestration(4.7×1.4mm)in the anterior medullary segment of the left PICA associated with an unruptured fusiform aneurysm(7.2×6.1mm)arising from the entire lateral limb of the fenestrated segment. The left VA aneurysm had a wide neck(7.2×6.8mm)and was located at the portion just distal to the bifurcation of the left PICA. The patient requested conservative management of both aneurysms because no significant change in the size or shape of either had been observed during the last 5 years. An extensive review of the literature revealed that nine cases of PICA fenestration have been reported. Among these, detailed medical records were described in seven cases, and an aneurysm at the fenestrated artery had been detected in only 2 cases. To our knowledge, this is the first report of a PICA fenestration associated with an unruptured aneurysm at the fenestrated segment. Embryologically, the PICA fenestration may represent a remnant of plexiform arterial channels between the primitive VA and primitive lateral vertebrobasilar anastomosis.
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http://dx.doi.org/10.11477/mf.1436204059DOI Listing
September 2019

[A Case of Dural Arteriovenous Fistula Involving the Superior Sagittal Sinus that Presented as a Primary Intraventricular Hemorrhage].

No Shinkei Geka 2019 Aug;47(8):859-867

Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center.

We report an extremely rare case of dural arteriovenous fistula(DAVF)involving the superior sagittal sinus(SSS)that presented as a primary intraventricular hemorrhage(PIVH). A 79-year-old man who presented with disturbance of consciousness and vomiting was transferred to our hospital. The initial head CT revealed an intraventricular hemorrhage in the lateral, third, and fourth ventricles, predominantly involving the right lateral ventricle associated with obstructive hydrocephalus. CT angiography and three-dimensional rotational angiography(3D-RA)revealed SSS-DAVF with retrograde venous drainage from the cortical venous system to the subependymal venous system through engorged superficial/anastomotic/deep medullary or transcerebral veins, showing a pseudophlebitic pattern. A severe stenosis of the SSS was observed at the site just proximal to the shunting point. A varix of the right transvers caudate vein(TCV)was observed within the thickest portion of the hematoma in close contact with the wall of the right lateral ventricle. A stenosis of the branching point of the right TCV was detected on the 3D-RA image. The DAVF was completely cured after transarterial embolization. The varix gradually shrank and finally disappeared after 2 months. This is the first report of a case of PIVH due to SSS-DAVF with a subependymal varix considered as the bleeding point. Serial gadolinium-enhanced MR images clearly showed the shrinking of the varix. Our case is the second reported case of spontaneous resolution of the varix after embolization of the DAVF. The obstructive changes of the two venous outflow pathways(SSS/TCV)might further worsen the state of venous congestion in the deep medullary venous system and eventually lead to formation and rupture of the varix.
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http://dx.doi.org/10.11477/mf.1436204037DOI Listing
August 2019

[A Rare Case of Spontaneous Thrombosis and Recanalization of a Ruptured Small Aneurysm in the Distal Posterior Inferior Cerebellar Artery].

No Shinkei Geka 2019 Jun;47(6):647-652

National Hospital Organization Nagasaki Medical Center.

The incidence of spontaneous thrombosis of intracranial aneurysm ranges from 1% to 2% of ruptured aneurysms. Most of them are giant or large aneurysms, and various factors have been discussed in previous literatures. Recanalization of thrombosed aneurysms may be rare, but its mechanism is poorly understood. Reports on recanalization of small aneurysms after spontaneous thrombosis are rare, and the natural history is still unknown. We describe a rare case of spontaneous thrombosis and recanalization of a ruptured small aneurysm of the distal posterior inferior cerebellar artery. Spontaneous aneurysmal thrombosis should not always be considered as a good or safe sign, as it may recanalize in a short time, resulting in re-rupture. In the acute stage, periodic follow-up of patients with a spontaneously thrombosed aneurysm is important.
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http://dx.doi.org/10.11477/mf.1436203999DOI Listing
June 2019

[A Rare Case of an Unruptured Aneurysm Arising from the Proximal End of the Fenestration of the Infracallosal Segment(A2)of the Anterior Cerebral Artery].

No Shinkei Geka 2019 May;47(5):565-572

Residency program, Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center.

We report an extremely rare case of a fenestration in the infracallosal(A2)segment of the right anterior cerebral artery(ACA)associated with an unruptured aneurysm at the proximal end of the fenestrated portion. A 70-year-old man was referred to our hospital for further examination and treatment of unruptured aneurysms at the A1/A2 junction of the right ACA and the distal end of the right vertebral artery that were incidentally detected on MR angiography. CT angiography and 3D-rotational angiography revealed a fenestration in the proximal A2 segment of the right ACA with a small(3.6×3.8mm)aneurysm arising from the proximal end of the fenestration. The dome of the aneurysm projected to the left anterior/inferior direction. He underwent aneurysm neck clipping surgery via the right pterional approach without complications, while the vertebral artery aneurysm was managed conservatively. An extensive review of the literature revealed that only a small number of cases of A2 fenestration have been reported to date. To our knowledge, this is the first report of an A2 fenestration associated with an aneurysm at the fenestrated segment. Embryologically, the A2 fenestration may represent a remnant of plexiform arterial channels that constitute the primitive ACA system including the primitive olfactory artery, median artery of the corpus callosum and anterior communicating plexus.
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http://dx.doi.org/10.11477/mf.1436203983DOI Listing
May 2019

Impaired comprehension of metaphorical expressions in very mild Alzheimer's disease.

Neuropsychiatr Dis Treat 2019 20;15:713-720. Epub 2019 Mar 20.

Department of Neurology, Kurashiki Heisei Hospital, Kurashiki, Okayama, Japan.

Background: Brain-damaged patients often have difficulty understanding non-literal language. However, whether patients with Alzheimer's disease (AD) have comprehension deficits of metaphorical expressions, in contrast with non-metaphorical (literal) expressions, remains unclear.

Patients And Methods: The subjects were 40 AD patients; 20 had mild AD (17-23 points on the Mini-Mental State Examination [MMSE]), and 20 had very mild AD (≥24 points). Twenty normal elderly controls were also enrolled as a control group. Thirty sentences that contained novel similes (Items) were prepared. For each Item, four explanatory choices, consisting of one correct response and three foils, were provided. The participants were asked to choose the written statement that best represented the Item's meaning. In addition, all the subjects completed the Token Test.

Results: The patients with mild AD had significantly lower scores than the normal controls on both the simile comprehension test and the Token Test. However, the patients with very mild AD exhibited significantly lower scores on the simile comprehension test, but not on the Token Test. The distributions of error types for the simile test differed between the mild AD group and the other groups. The mild AD patients made more errors that were "far" from the correct responses.

Conclusion: Patients with AD are more likely to have comprehension deficits of metaphorical expressions than comprehension deficits of non-metaphorical expressions. Pragmatic language dysfunction may precede formal language dysfunction during the progression of AD.
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http://dx.doi.org/10.2147/NDT.S193645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430997PMC
March 2019

[A Rare Case of an Unruptured Aneurysm Arising from the Proximal End of the Fenestration of the Cavernous Segment of the Internal Carotid Artery].

No Shinkei Geka 2019 Feb;47(2):217-223

Residency Program, Department of Neurosurgery, National Hospital Organization, Nagasaki Medical Center.

We report an extremely rare case of a fenestration in the cavernous segment of the left internal carotid artery(ICA)associated with an unruptured aneurysm at the proximal end of the fenestrated portion. A 44-year-old woman with a dull headache was referred to our hospital for further evaluation of a suspected aneurysm in the right ICA on MR angiography(MRA). CT angiography and 3D-rotational angiography revealed no aneurysm in the right ICA;however, an intracavernous fenestration with an incidental aneurysm was observed in the left ICA. The aneurysm was small(5×3mm)with a wide neck arising from the origin of the ventral limb of the duplicated vessels, in association with a tiny bulge projecting medially. She requested conservative management and periodic follow-up with MRA. After 18 months, no structural change in the aneurysm was observed. To our knowledge, including our patient, only three cases of this type of ICA fenestration have been published, and this is the first report of an ICA fenestration with an unruptured aneurysm at the fenestrated segment. It is presently unknown whether the intracavernous fenestration has the potential to form an aneurysm within the proximal end of the duplicated segment, as reported in cases of supraclinoid ICA fenestrations.
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http://dx.doi.org/10.11477/mf.1436203921DOI Listing
February 2019

[Unruptured Aneurysm Arising from the Proximal End of the Duplicate Origin of the Middle Cerebral Artery].

No Shinkei Geka 2018 Oct;46(10):901-909

Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center.

We report a rare case of an unruptured aneurysm arising from the junction between the internal carotid artery(ICA)and duplicate origin of the middle cerebral artery(MCA). A 49-year-old man who presented with vertigo was admitted to our hospital. Subsequent MR and CT angiograms revealed an incidental aneurysm arising from the proximal end of the duplicate origin of the left MCA. He underwent clipping via the distal transsylvian approach. The aneurysm projected to the posterior direction and several perforators from the two M1 segments were attached to the neck of the aneurysm, which made neck dissection very difficult. Approaching the space from the posterior/lateral direction to reach the M1 segment, the aneurysm neck was successfully dissected and clipped without sacrificing any perforators or stenosis of parent vessels. The postoperative course was uneventful, and the patient was discharged within 2 weeks. Duplicate origin of the MCA has been confused with a fenestration of the proximal M1 segment or terminal segment of the ICA. In this condition, two MCA branches arise separately from the terminal segment of the ICA and fuse early to form an arterial ring at the proximal M1 segment. An aneurysm originating from this anomaly has never been described. However, some aneurysms associated with this type of origin may have incorrectly been reported as those associated with proximal MCA or terminal ICA fenestrations. We summarize the cases that are similar to our case of duplicate origin of the MCA with an aneurysm, and discuss the precise diagnosis and significant intraoperative problems that were described in the literature.
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http://dx.doi.org/10.11477/mf.1436203837DOI Listing
October 2018

[Aging and verbal memory -an experimental study using structured and non-structured word lists].

Nihon Ronen Igakkai Zasshi 2018 ;55(1):117-123

Department of Occupational Therapy, Okayama Institute for the Medical and Technical Science.

Aim: Typical neuropsychological methods for measuring the verbal memory function include the Rey Auditory Verbal Learning Test (AVLT) and the California Verbal Learning Test (CVLT). The stimulus words of the CVLT are structured according to their semantic categories, and many researchers have claimed that the CVLT can also evaluate subjects' memory strategy. However, the stimulus words of these tests do not have equal difficulty, which is necessary when comparing their performances directly, and there are no standard word lists for them in Japanese. In this study, we developed two word lists with the same number and difficulty of stimulus words in order to examine the effects of aging on the comprehension of structured word lists.

Methods: A non-structured (NS) verbal memory test to represent the AVLT and a structured (S) test to represent the CVLT were developed. The subjects were 40 healthy young adults (18-25 years of age) and 40 healthy elderly individuals (65-80 years of age).

Results: The results revealed that the elderly group correctly recalled significantly fewer words than the young group. The elderly group demonstrated a significantly higher rate of word loss due to interference. The number of correctly recalled words in the elderly group was significantly more for the S test than for the NS test, which was not the case in the young group.

Conclusions: Since elderly people have a poorer verbal memory than younger people, they gain more benefit from the S test, in which the word list is structured and subjects may be able to use memory strategies more easily. This is the first study in Japan to present standardized word lists for list-learning tasks and their normative data in different age groups.
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http://dx.doi.org/10.3143/geriatrics.55.117DOI Listing
April 2019

[Aging and verbal memory -an experimental study using structured and non-structured word lists].

Nihon Ronen Igakkai Zasshi 2018 ;55(1):117-123

Department of Occupational Therapy, Okayama Institute for the Medical and Technical Science.

Aim: Typical neuropsychological methods for measuring the verbal memory function include the Rey Auditory Verbal Learning Test (AVLT) and the California Verbal Learning Test (CVLT). The stimulus words of the CVLT are structured according to their semantic categories, and many researchers have claimed that the CVLT can also evaluate subjects' memory strategy. However, the stimulus words of these tests do not have equal difficulty, which is necessary when comparing their performances directly, and there are no standard word lists for them in Japanese. In this study, we developed two word lists with the same number and difficulty of stimulus words in order to examine the effects of aging on the comprehension of structured word lists.

Methods: A non-structured (NS) verbal memory test to represent the AVLT and a structured (S) test to represent the CVLT were developed. The subjects were 40 healthy young adults (18-25 years of age) and 40 healthy elderly individuals (65-80 years of age).

Results: The results revealed that the elderly group correctly recalled significantly fewer words than the young group. The elderly group demonstrated a significantly higher rate of word loss due to interference. The number of correctly recalled words in the elderly group was significantly more for the S test than for the NS test, which was not the case in the young group.

Conclusions: Since elderly people have a poorer verbal memory than younger people, they gain more benefit from the S test, in which the word list is structured and subjects may be able to use memory strategies more easily. This is the first study in Japan to present standardized word lists for list-learning tasks and their normative data in different age groups.
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http://dx.doi.org/10.3143/geriatrics.55.117DOI Listing
April 2019

[Aging and verbal memory -an experimental study using structured and non-structured word lists].

Nihon Ronen Igakkai Zasshi 2018 ;55(1):117-123

Department of Occupational Therapy, Okayama Institute for the Medical and Technical Science.

Aim: Typical neuropsychological methods for measuring the verbal memory function include the Rey Auditory Verbal Learning Test (AVLT) and the California Verbal Learning Test (CVLT). The stimulus words of the CVLT are structured according to their semantic categories, and many researchers have claimed that the CVLT can also evaluate subjects' memory strategy. However, the stimulus words of these tests do not have equal difficulty, which is necessary when comparing their performances directly, and there are no standard word lists for them in Japanese. In this study, we developed two word lists with the same number and difficulty of stimulus words in order to examine the effects of aging on the comprehension of structured word lists.

Methods: A non-structured (NS) verbal memory test to represent the AVLT and a structured (S) test to represent the CVLT were developed. The subjects were 40 healthy young adults (18-25 years of age) and 40 healthy elderly individuals (65-80 years of age).

Results: The results revealed that the elderly group correctly recalled significantly fewer words than the young group. The elderly group demonstrated a significantly higher rate of word loss due to interference. The number of correctly recalled words in the elderly group was significantly more for the S test than for the NS test, which was not the case in the young group.

Conclusions: Since elderly people have a poorer verbal memory than younger people, they gain more benefit from the S test, in which the word list is structured and subjects may be able to use memory strategies more easily. This is the first study in Japan to present standardized word lists for list-learning tasks and their normative data in different age groups.
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http://dx.doi.org/10.3143/geriatrics.55.117DOI Listing
April 2019

Predictors for delayed encephalopathy following acute carbon monoxide poisoning.

BMC Emerg Med 2014 Jan 31;14. Epub 2014 Jan 31.

Department of Neuropsychiatry, Iwate Medical University, school of Medicine, Morioka, Iwate, Japan.

Background: In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether "delayed neuropsychiatric sequelae (DNS)" will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases.

Methods: This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc.

Results: Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions.

Conclusion: In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks' follow-up to watch for the development of DNS is considered necessary.
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http://dx.doi.org/10.1186/1471-227X-14-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909505PMC
January 2014

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Seishin Shinkeigaku Zasshi 2013 ;115(5):485-91

Department of Disaster and Community Psychiatry, School of Medicine, Iwate Medical University.

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.
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September 2013

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Seishin Shinkeigaku Zasshi 2013 ;115(5):485-91

Department of Disaster and Community Psychiatry, School of Medicine, Iwate Medical University.

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.
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September 2013

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Seishin Shinkeigaku Zasshi 2013 ;115(5):485-91

Department of Disaster and Community Psychiatry, School of Medicine, Iwate Medical University.

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.
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September 2013

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Seishin Shinkeigaku Zasshi 2013 ;115(5):485-91

Department of Disaster and Community Psychiatry, School of Medicine, Iwate Medical University.

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.
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September 2013

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Seishin Shinkeigaku Zasshi 2013 ;115(5):485-91

Department of Disaster and Community Psychiatry, School of Medicine, Iwate Medical University.

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.
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September 2013

DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2-hexenal in vitro and their analysis in mouse and human DNA.

Chem Res Toxicol 2010 Mar;23(3):630-6

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.
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http://dx.doi.org/10.1021/tx9003819DOI Listing
March 2010

Discovery of incednine as a potent modulator of the anti-apoptotic function of Bcl-xL from microbial origin.

J Am Chem Soc 2008 Feb 19;130(6):1822-3. Epub 2008 Jan 19.

Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.

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http://dx.doi.org/10.1021/ja710124pDOI Listing
February 2008

Identification of 4-oxo-2-hexenal and other direct mutagens formed in model lipid peroxidation reactions as dGuo adducts.

Chem Res Toxicol 2006 Jan;19(1):130-8

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health (UOEH), 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

We searched for mutagens that react with 2'-deoxyguanosine (dGuo) in model systems of lipid peroxidation. To autoxidation systems of methyl linoleate (model of omega-6 fat), methyl alpha-linolenate (MLN) (model of omega-3 fat), and commercial salad oil, dGuo was added. The reaction mixtures were analyzed by HPLC. Six adducts were detected, and their structures were determined by 1H and 13C NMR, UV, and mass spectra and by comparison with synthetic authentic samples. The mutagens that reacted with dGuo to form these adducts were proposed as glyoxal, glyoxylic acid, ethylglyoxal, and 4-oxo-2-hexenal (4-OHE). The formation of 8-hydroxy-dGuo, an oxidized product of dGuo, was also detected in the model reaction mixtures. Among them, glyoxal and glyoxylic acid are known mutagens, while ethylglyoxal and 4-OHE, produced from MLN, have not been reported as mutagens thus far. We confirmed the mutagenic activity of 4-OHE with Salmonella strains, TA100 and TA104, without S9 mix. These compounds may be involved in lipid peroxide-related cancers.
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http://dx.doi.org/10.1021/tx050236mDOI Listing
January 2006

4-oxo-2-hexenal, a mutagen formed by omega-3 fat peroxidation, causes DNA adduct formation in mouse organs.

Ind Health 2005 Oct;43(4):699-701

Department of Environmental Oncology, Institute of Industrial Ecological Sciences University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

To identify mutagens formed in a model reaction of lipid peroxidation, linolenic acid methyl ester and hemin were reacted with dG. As a result, a 4-oxo-2-hexenal-dG adduct (dG*) was identified in the model reaction mixture. The 4-oxo-2-hexenal (4-OHE) showed mutagenic activity in the Salmonella typhimurium strains TA100 and TA104. After 4-OHE was orally administered to mice, dG, 4-OHE-dC- and 4-OHE-5-methyl-dC adducts were detected in esophageal, stomach and intestinal DNA. In the vapor phase released from the methyl linolenate-hemin model system, and in the smoke released during the broiling of fish, 4-OHE was detected by GCMS. The 4-OHE seems to be produced by the auto-oxidation of omega-3 polyunsaturated fatty acids. These results provide a warning to workers dealing with omega-3 fats, who may be exposed to this volatile mutagen.
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http://dx.doi.org/10.2486/indhealth.43.699DOI Listing
October 2005

Caprazamycins, novel lipo-nucleoside antibiotics, from Streptomyces sp. II. Structure elucidation of caprazamycins.

J Antibiot (Tokyo) 2005 May;58(5):327-37

Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

Novel antibiotics, active against acid-fast bacteria, caprazamycins, were isolated from the culture broth of Streptomyces sp. MK730-62F2. The planar structures of the compounds were determined by 2D NMR spectroscopic study. Furthermore, the absolute structure of caprazamycin B (2) was established by NMR spectroscopy and X-ray crystallography of its degradation products and by total synthesis of the 5-amino-5-deoxy-D-ribose moiety. In the course of degradation studies of 2 under alkaline and acidic conditions, we obtained the two core components, caprazene (11) and caprazol (14), respectively, in high yield. Structurally, caprazamycins belong to a family of lipouridyl antibiotics, which have been discovered as specific inhibitors of a bacterial translocase.
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http://dx.doi.org/10.1038/ja.2005.41DOI Listing
May 2005

Absolute configuration of kigamicins A, C and D.

J Antibiot (Tokyo) 2005 Jan;58(1):56-60

Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, Numazu-shi, Shizuoka 410-0301, Japan.

The stereochemistry of kigamicins A (1), C (2) and D (3) were elucidated by a combination of X-ray crystallographic analysis and degradation studies. The absolute structures of kigamicins thus determined were depicted as shown in Fig. 2.
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http://dx.doi.org/10.1038/ja.2005.6DOI Listing
January 2005

First synthesis and determination of the absolute configuration of sulphostin, a novel inhibitor of dipeptidyl peptidase IV.

J Nat Prod 2004 Jun;67(6):999-1004

Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

Sulphostin, a novel dipeptidyl peptidase IV (DPP-IV) inhibitor, was isolated from the culture broth of Streptomyces sp. MK251-43F3. Determination of the absolute configurations of two asymmetric atoms using the natural product was not achieved due to the small amount of the compound obtained. We synthesized four possible stereoisomers of sulphostin from D- or L-ornithine and compared their physicochemical and biological data to naturally isolated sulphostin. As a result, the absolute configurations at C-3 and the phosphorus atom of sulphostin were determined to be S and R, respectively, by X-ray crystallography. Synthetic sulphostin and its C-3 epimer have strong inhibitory activities against DPP-IV, IC50 values of which are 6.0 and 8.9 ng/mL, respectively. Thus it appears that the configuration of the phosphorus atom is primarily responsible for the activity; in contrast, the configuration of C-3 does not appear to affect the activity.
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http://dx.doi.org/10.1021/np030491bDOI Listing
June 2004

Two cases of functional focal retrograde amnesia with impairment of object use.

Cortex 2002 Sep;38(4):613-22

Department of Welfare System and Health Science, Okayama Prefectural University, Soja, Japan.

We report on two patients, TH and KN, with focal retrograde amnesia (FRA). Their memory loss regarding life events extended to their whole lives, whereas they could acquire and retain new information. They also showed prominent deficits in production and comprehension of common words. In addition, at least in the testing situation, they were impaired in their recognition and use of familiar objects. Although both cases of FRA followed an episode that can cause brain pathology, MRI revealed no structural abnormality in either patient. Stressful situations preceding the onset were evident in KN, but not in TH. We discuss their impairments of object knowledge from a neuropsychological perspective, and we interpret the etiology of their condition as a functional rather than a psychogenic amnesia.
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http://dx.doi.org/10.1016/s0010-9452(08)70025-xDOI Listing
September 2002

Panepophenanthrin, from a mushroom strain, a novel inhibitor of the ubiquitin-activating enzyme.

J Nat Prod 2002 Oct;65(10):1491-3

Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

Screening for inhibitors of the ubiquitin-proteasome pathway, considered to regulate important cellular events and linked to serious diseases as well, led to isolation of a new compound, panepophenanthrin, from the fermented broth of a mushroom strain, Panus rudis Fr. IFO 8994. This is the first inhibitor of the ubiquitin-activating enzyme, which is indispensable for the ubiquitin-proteasome pathway. The structure of panepophenanthrin was determined by NMR and X-ray crystallographic analyses as 1,3a,10-trihydroxy-10c-(3-hydroxy-3-methylbut-1-enyl)-5,5-dimethyl-1,2,3,3a,5,5a,8,9,10,10a,10b,10c-dodecahydro-4-oxa-2,3,8,9-diepoxyacephenanthrylen-7-one.
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http://dx.doi.org/10.1021/np020098qDOI Listing
October 2002
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