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"Kawamata, Takakazu"
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Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum
2019
Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.
Journal Article
Prediction of lower-grade glioma molecular subtypes using deep learning
by
Nitta Masayuki
,
Fukuya Yasukazu
,
Saito Taiichi
in
Accuracy
,
Classification
,
Computed tomography
2020
IntroductionIt is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively.MethodsA deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients.ResultsThe model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly.ConclusionsA deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype.
Journal Article
Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures
by
Seiichiro, Eguchi
,
Takakazu, Kawamata
,
Yasuo, Aihara
in
Anticonvulsants
,
Child
,
Epilepsies, Partial
2023
Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.
Journal Article
Correction: Onodera et al. Prognostic Factors and Talaporfin Sodium Concentration in Photodynamic Therapy for Recurrent Grade 4 Glioma. Pharmaceuticals 2025, 18, 583
2025
In the original publication [...]
Journal Article
Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid
by
Chiba Kentaro
,
Aihara Yasuo
,
Kawamata Takakazu
in
Alkaline phosphatase
,
Basal ganglia
,
Biopsy
2021
PurposeThe disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF).MethodsTwenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment.ResultsThe mean follow-up period was 76.0 months (range, 3–168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%.ConclusionOur data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.
Journal Article
Prognostic Factors and Talaporfin Sodium Concentration in Photodynamic Therapy for Recurrent Grade 4 Glioma
2025
Background: Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. Methods: Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women’s Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. Results: Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93–0.99], p = 0.01) and Alb (3.68 [1.05–13.76], p = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival (p = 0.0454). RNA-seq analysis indicated decreased expression of ACTB and PDPN genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. Conclusions: TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity.
Journal Article
Application of indocyanine green fluorescence endoscopic system in transsphenoidal surgery for pituitary tumors
2019
BackgroundFor the precise removal of pituitary tumors, preserving the surrounding normal structures, we need real-time intraoperative information on tumor location, margins, and surrounding structures. The aim of this study was to evaluate the benefits of a new intraoperative real-time imaging modality using indocyanine green (ICG) fluorescence through an endoscopic system during transsphenoidal surgery (TSS) for pituitary tumors.MethodsBetween August 2013 and October 2014, 20 patients with pituitary and parasellar region tumors underwent TSS using the ICG fluorescence endoscopic system. We used a peripheral vein bolus dose of 6.25 mg/injection of ICG, started with a time counter, and examined how each tissue type increased and decreased in fluorescence through time.ResultsA total of 33 investigations were performed for 20 patients: 9 had growth hormone secreting adenomas, 6 non-functioning pituitary adenomas, 3 Rathke’s cleft cysts, 1 meningioma, and 1 pituicytoma. After the injection of ICG, the intensity of fluorescence of tumor and normal tissues under near-infrared light showed clear differences. We could differentiate tumor margins from adjacent normal tissues and define clearly the surrounding normal structures using the different fluorescent intensities time changes and tissue-specific fluorescence patterns.ConclusionsThe ICG endoscopic system is simple, user-friendly, quick, cost-effective, and reliable. The method offered real-time information during TSS to delimit pituitary and parasellar region tumor tissue from surrounding normal structures. This method can contribute to the improvement of total removal rates of tumors, reduction of complications after TSS, saving surgical time, and preserving endocrinological functions.
Journal Article
Complex regional pain syndrome after mRNA-based COVID-19 vaccination
by
Horisawa, Shiro
,
Ando, Tamon
,
Kawamata, Takakazu
in
Adolescent
,
Baclofen
,
Baclofen - therapeutic use
2023
We describe the case of a 17-year-old woman diagnosed with complex regional pain syndrome (CRPS) at a pain clinic after the second dose of the COVID-19 vaccine. She was referred to our department for surgical treatment of movement disorder seven months after the second inoculation. Baclofen (50 µg), administered intrathecally, improved the involuntary movements of her right hand. After administration of zolpidem (5 mg), involuntary movements of the right index finger almost disappeared. However, neither zolpidem nor intrathecal baclofen improved the limited range of motion of the first joint of the left-hand finger. Despite various reports on CRPS development after vaccination, only one case post COVID-19 vaccination has been reported. Therefore, healthcare providers should keep in mind that CRPS can appear after the COVID-19 vaccination.
•There have been various reports of CRPS after vaccination.•Here, a 17-year-old woman presented with CRPS after second COVID vaccination.•Healthcare providers should be aware that CRPS can occur after COVID vaccination.
Journal Article
Tumor recurrence patterns after surgical resection of intracranial low-grade gliomas
2019
Introduction
Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis.
Methods
Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years.
Results
Early (within 2 years after primary surgery) and non-early (> 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow ( > 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD,
IDH1
-mutant DA, and
IDH
wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG.
Conclusions
Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.
Journal Article
Occipital artery–posterior inferior cerebellar artery bypass for anterior inferior cerebellar artery stenosis with repeated cerebellar ischemic stroke: a case report
2025
Background
Vertebrobasilar insufficiency revascularization has long been a preventive treatment for cerebral infarction. However, no studies have demonstrated the efficacy of revascularization in patients with cerebellar ischemia.
Case presentation
We present the case of a 77-year-old Japanese man who experienced seven recurrent cerebellar infarctions over 2 years. Severe stenosis was noted at the origin of the common trunk of the posterior inferior cerebellar artery and anterior inferior cerebellar artery. Patients with cerebral infarctions are resistant to medical treatment. Blood flow evaluation showed that the area of reduced cerebrovascular reactivity corresponded to the area where repeated small infarctions occurred. An occipital artery–posterior inferior cerebellar artery bypass was performed to prevent another infarction. Postoperative single-photon emission computed tomography showed an improved cerebrovascular reactivity. No ischemic events occurred during 2 years of a postoperative follow-up period.
Conclusion
Occipital artery–posterior inferior cerebellar artery bypass is an effective treatment method for vascular stenosis and decreased blood circulation due to posterior circulation ischemia.
Journal Article