Clinical implications of DLL4 expression in gastric cancer

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor neovascular development and angiogenesis during tumor growth. The clinical significance of DLL4 expression in gastric cancer has not been clarified. METHODS: Gastric cancer cell lines and 180 gastric cancer patients were enrolled. DLL4 expression in gastric cancer cells and stroma was identified and evaluated immunohistochemically. The association between DLL4 and clinicopathological factors was also assessed. RESULTS: DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells by immunoblotting and immunohistochemical staining. DLL4 positivity in cancer cells and stroma was found in 88 (48%) and 41 (22%) of the 180 gastric cancer patients respectively. Both cancer and stromal DLL4 expression significantly correlated with more advanced tumor depth, nodal involvement, and lymphatic and venous invasion. A strongly positive association between cancerous and stromal DLL4 expression was identified (p < 0.01). Both cancerous and stromal DLL4 expression were prognostic markers in gastric cancer as determined by univariate analysis. CONCLUSIONS: Cancerous and stromal DLL4 expression was found in 48% and 22% in gastric cancer, and significantly affected postoperative clinical outcomes. Cancerous and stromal DLL4 expression may be an effective target of anti-DLL4 treatment in gastric cancer

Determination of specific ion positions of Cr³⁺ and O²- in Cr₂O₃ thin films and their relationship to exchange anisotropy at Co/Cr₂O₃ interfaces

The structures of antiferromagnetic Cr₂O₃(0001) thin films with perpendicular exchange bias were investigated using reflection high-energy electron diffraction, X-ray reflectivity, and synchrotron X-ray diffraction. We mainly investigated the specific ion positions of Cr³⁺ and O²- in the corundum structure and discussed their relationship to the magnetic anisotropy of Cr₂O₃. The Cr₂O₃(0001) thin film grown on a Pt(111) buffer layer exhibited a perpendicular exchange anisotropy density of 0.42 mJ/m², in which the Cr³⁺ position is the primary factor in the enhancement of magnetic anisotropy due to dipolar-interaction. In contrast, the single-crystalline Cr₂O₃(0001) film grown on a α-Al₂O₃(0001) substrate featured a low exchange magnetic anisotropy of 0.098 mJ/m². In this film, the Cr³⁺ position parameter is an insignificant factor, leading to low magnetic anisotropy. The O²- ion position also differs between the two types of films, which can affect both the magnetic anisotropy energy originating from fine structures and the magneto-electric properties of Cr₂O₃.Yu Shiratsuchi, Yuuta Nakano, Nobuhito Inami, Tetsuro Ueno, Kanta Ono, Reiji Kumai, Ryoko Sagayama, and Ryoichi Nakatani, Journal of Applied Physics 123, 103903 (2018); https://doi.org/10.1063/1.5020620

Enhancement of perpendicular exchange bias by introducing twin boundary in Pt/Co/α-Cr₂O₃/α-V₂O₃ epitaxial film

Perpendicular exchange anisotropy at the Co/α-Cr₂O₃ interface was investigated using the two types of films: the film with the single crystalline α-Cr₂O₃ and that with the twinned a-Cr₂O₃. Exchange anisotropy energy density JK of the film with the single crystalline α-Cr₂O₃ was ~0.09 erg/cm² whereas JK of the film with the twinned α-Cr₂O₃ was ~0.43 erg/cm², more than 4-times enhancement. We discussed the mechanism of the enhancement of JK based on the exchange coupling at the twin boundary and that the spin frustration at the twin boundary can be the origin of the enhancement of JK.Y.Shiratsuchi, S.Yoshida, S.Onoue, et al. Enhancement of perpendicular exchange bias by introducing twin boundary in Pt/Co/a-Cr₂O₃/a-V₂O₃ epitaxial film. Materials Transactions 60, 2028 (2019); https://doi.org/10.2320/matertrans.MT-M2019102

Assessment of human stress and depression by DNA microarray analysis

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects

Interface atomic structures and magnetic anisotropy of Fe and Pd/Fe monatomic films on Pd(001)

The magnetic anisotropy of monatomic Fe films on Pd(001) with or without a Pd overlayer was investigated from the standpoint of interface atomic structures. Quantitative analysis included low-energy electron diffraction and x-ray magnetic circular dichroism (XMCD) experiments, and first-principles calculations were also performed on monatomic Fe and Pd/Fe systems. It was revealed that Fe atoms intermix with the Pd substrate at room temperature. A spin reorientation transition occurs at a critical Fe thickness of 1.2 monolayers (ML) in Fe/Pd(001), while in-plane magnetic anisotropy is persistent in Pd/Fe/Pd(001) throughout the entire sample. The Fe 3d spin and orbital magnetic moments for both systems are strongly enhanced near 1 ML Fe thickness, as compared to those of the bulk iron crystal. In addition, an induced magnetic moment in interfacial Pd atoms was observed by XMCD at the Pd M2,3 core absorption edges. It was concluded that the L10-like tetragonally distorted interface atomic structure in monatomic Fe/Pd(001) induces the perpendicular magnetic anisotropy

Mental changes in PD with STN-DBS

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease(PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n=13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at one and six months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the verbal fluency test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p<0.001) and HAM-A score (p=0.004) showed significant improvement at one month post-surgery, but a significant decline was observed in the WCST total error (p=0.005) and the semantic VFT score (p<0.001). The phonetic VFT also showed a substantial decline (p=0.015) at one month post-surgery. At six months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms

ABCA7 Gene Expression and Genetic Association Study in Schizophrenia

Introduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimer’s disease, the relationship between ABCA7 and schizophrenia has been unknown. Methods: Schizophrenia patients (n = 50; 24 males, 62.1 ± 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area. Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner. Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia

Mental changes in PD with STN-DBS

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease(PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n=13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at one and six months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the verbal fluency test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p<0.001) and HAM-A score (p=0.004) showed significant improvement at one month post-surgery, but a significant decline was observed in the WCST total error (p=0.005) and the semantic VFT score (p<0.001). The phonetic VFT also showed a substantial decline (p=0.015) at one month post-surgery. At six months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms

TREM2 Expression in Schizophrenia

TREM2 and TYROBP are causal genes for Nasu–Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer’s disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia. Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia. Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P < 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients. Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders