subacute combined spinal cord degeneration

We report a case of subacute combined spinal cord degeneration (SCD) caused by vegetarianism and autoimmune gastritis, which is rarely reported in Japan, and which showed improvement in symptoms and imaging findings after vitamin B12 administration. As delayed treatment can lead to irreversible damage, we suggest that patients with characteristic abnormal signals in the posterior cervical cord should be examined while considering the possibility that SCD may occur even in the absence of a history of gastrectomy or heavy drinking. We also describe the patient’s reversible abnormal signals in the cerebral white matter on magnetic resonance imaging, indicative of an early sign of leukoencephalopathy associated with vitamin B12 deficiency

Neuroanatomical correlates of attention-deficit-hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention-deficit-hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel-based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age-and gender-matched typically developing subjects underwent high-spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel-by-voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.ArticlePSYCHIATRY AND CLINICAL NEUROSCIENCES. 64(4):394-402 (2010)journal articl

Pharmacokinetic–pharmacodynamic analysis of cefmetazole against extended-spectrum β-lactamase-producing Enterobacteriaceae in dogs using Monte Carlo Simulation

IntroductionThe spread of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is a serious concern in companion animal medicine owing to their ability to develop multidrug resistance. Cefmetazole (CMZ) is a candidate drug for treating ESBL-E infections; however, its regimen in dogs has not been established. In this study, we investigated the pharmacokinetic (PK) indices of CMZ in dogs and performed PK–pharmacodynamic (PD) analyses using Monte Carlo Simulation (MCS).MethodsIn total, six healthy dogs received an intravenous bolus dose of CMZ (40 mg/kg body weight). Serum CMZ concentrations were evaluated using liquid chromatography–mass spectrometry, and PK indices were determined based on non-compartmental analysis. The PK–PD cut-off (COPD) values were calculated as the highest minimum inhibitory concentration (MIC) that achieved ≥90% probability of target attainment for a target value of unbounded drug concentration exceeding 40% of the dosing interval. The cumulative fraction of response (CFR) was calculated based on the MIC distribution of wild-type ESBL-E from companion animals.ResultsThe area under the concentration–time curve and elimination half-time were 103.36 ± 7.49 mg·h/L and 0.84 ± 0.07 h, respectively. MCS analysis revealed that COPD values for regimens of 40 mg/kg q12, q8h, and q6h were ≤ 0.5, ≤2, and ≤ 4 μg/mL, respectively. A regimen of 40 mg/kg q6h was estimated to achieve a CFR of 80–90% for Escherichia coli and Klebsiella pneumoniae. By contrast, all regimens exhibited a CFR of ≤70% for Proteus mirabilis and Enterobacter cloacae.DiscussionWe conclude that CMZ at 40 mg/kg q6h could be a viable treatment regimen for dogs infected with ESBL-producing Escherichia coli and Klebsiella pneumoniae

Imaging features of a myoepithelial carcinoma of the nasal cavity : A case report and literature review

Myoepithelial carcinoma of the nasal cavity is extremely rare. We report the case of a 66-year-old man with myoepithelial carcinoma of the nasal cavity. Computed tomography (CT) and magnetic resonance imaging revealed a lobulated soft tissue mass with central necrosis and hemorrhage, as well as an invasion of the skull base and left orbit. The patient presented with continuous nasal congestion and heavy head and had no elevated level of squamous cell carcinoma-related antigen. CT, magnetic resonance imaging, or 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT revealed no evidence of a metastatic lesion. 18F-FDG accumulation in the tumor was inhomogeneous and moderate. Histopathological examination of the resected specimen confirmed a well-circumscribed solid tumor with septa, a small area of hemorrhage, and necrosis. The subsequent diagnosis was a myoepithelial carcinoma of the left nasal cavity. This case shows that nasal myoepithelial carcinoma might appear as a well-defined lobulated mass with hemorrhagic necrosis and intense contrast enhancement in the solid component. We conjecture that hemorrhagic necrosis and intense enhancement values may be potential markers of nasal myoepithelial carcinoma

Explanation of hand, foot, and mouth disease cases in Japan using Google Trends before and during the COVID-19: infodemiology study

[Background] Coronavirus Disease 2019 (COVID-19) pandemic affects common diseases, but its impact on hand, foot, and mouth disease (HFMD) is unclear. Google Trends data is beneficial for approximate real-time statistics and because of ease in access, is expected to be used for infection explanation from an information-seeking behavior perspective. We aimed to explain HFMD cases before and during COVID-19 using Google Trends. [Methods] HFMD cases were obtained from the National Institute of Infectious Diseases, and Google search data from 2009 to 2021 in Japan were downloaded from Google Trends. Pearson correlation coefficients were calculated between HFMD cases and the search topic “HFMD” from 2009 to 2021. Japanese tweets containing “HFMD” were retrieved to select search terms for further analysis. Search terms with counts larger than 1000 and belonging to ranges of infection sources, susceptible sites, susceptible populations, symptoms, treatment, preventive measures, and identified diseases were retained. Cross-correlation analyses were conducted to detect lag changes between HFMD cases and search terms before and during the COVID-19 pandemic. Multiple linear regressions with backward elimination processing were used to identify the most significant terms for HFMD explanation. [Results] HFMD cases and Google search volume peaked around July in most years, excluding 2020 and 2021. The search topic “HFMD” presented strong correlations with HFMD cases, except in 2020 when the COVID-19 outbreak occurred. In addition, the differences in lags for 73 (72.3%) search terms were negative, which might indicate increasing public awareness of HFMD infections during the COVID-19 pandemic. The results of multiple linear regression demonstrated that significant search terms contained the same meanings but expanded informative search content during the COVID-19 pandemic. [Conclusions] The significant terms for the explanation of HFMD cases before and during COVID-19 were different. Awareness of HFMD infections in Japan may have improved during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. The public interest reflected in information-seeking behavior can be helpful for public health surveillance

A Proteomic Approach for Comprehensively Screening Substrates of Protein Kinases Such as Rho-Kinase

BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity

Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study

BackgroundIn typical patients with multiple system atrophy with predominant parkinsonism (MSA-P) levodopa is ineffective. However, there are some of these patients who respond well to levodopa treatment. Levodopa efficacy in MSA-P patients is thought to be related to the degree of putaminal damage, but the pathological causation between the putaminal involvement and levodopa efficacy has not been established in detail.ObjectiveThis study aimed to evaluate the neuropathological features of the nigrostriatal dopaminergic system in a “levodopa-responsive” MSA-P patient in comparison with “levodopa-unresponsive” conventional MSA-P patients.Materials and methodsClinicopathological findings were assessed in a 53-year-old Japanese man with MSA who presented with asymmetric parkinsonism, levodopa response, and later wearing-off phenomenon. During autopsy, the nigrostriatal pathology of presynaptic and postsynaptic dopaminergic receptor density and α-synuclein status were investigated. The other two patients with MSA-P were examined using the same pathological protocol.ResultsFour years after the onset, the patient died of sudden cardiopulmonary arrest. On autopsy, numerous α-synuclein-positive glial cytoplasmic inclusions in the basal ganglia, pons, and cerebellum were identified. The number of neurons in the putamen and immunoreactivity for dopamine receptors were well-preserved. In contrast, significant neuronal loss and decreased dopamine receptor immunoreactivity in the putamen were observed in the “levodopa-unresponsive” MSA-P control patients. These putaminal pathology results were consistent with the findings of premortem magnetic resonance imaging (MRI). All three patients similarly exhibited severe neuronal loss in the substantia nigra and decreased immunoreactivity for dopamine transporter.ConclusionLevodopa responsiveness in patients with MSA-P may be corroborated by the normal putamen on MRI and the preserved postsynaptic nigrostriatal dopaminergic system on pathological examination. The results presented in this study may provide a rationale for continuation of levodopa treatment in patients diagnosed with MSA-P

Combination of Paeoniae Radix and Cnidii Rhizoma Prolonged Survival of Fully Mismatched Cardiac Allografts and Generated Regulatory Cells in Mice

In previous studies, we have demonstrated that Tokishakuyakusan (TJ-23) can prolong the survival of allogeneic cardiac grafts and induce regulatory T cells. In this study we investigated the effects of Paeoniae radix and Cnidii rhizoma, two components of TJ-23, on alloimmune responses in a murine cardiac transplantation model and whether the two agents have synergistic effect. CBA mice underwent transplantation of a C57BL/6 heart and received oral administration of 2 g/kg/day of Paeoniae radix, Cnidii rhizoma, or the mixture of two agents from the day of transplantation until 7 days afterward. Naïve CBA mice rejected C57BL/6 cardiac graft acutely (median survival time (MST): 7 days). Paeoniae radix and Cnidii rhizoma prolonged C57BL/6 allograft survival (MSTs: 13.5 and 15.5 days, resp.). However, the mixture of two agents prolonged C57BL/6 allograft survival indefinitely (MST > 100 days). Secondary CBA recipients given whole splenocytes from primary combination-treated CBA recipients with B6 cardiac allografts 30 days after grafting had prolonged survival of B6 hearts (MST: 33 days). Flow cytometry studies showed that the CD4+CD25+Foxp3+ regulatory cell population was increased in combination-treated recipients. Combination of Paeoniae radix and Cnidii rhizoma induced hyporesponsiveness to fully allogeneic cardiac allografts and may generate CD4+CD25+Foxp3+ regulatory cells in our model

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Jurkat Cells Using Bio-phantoms

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis

Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes

Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy