Osteopetrotic (op/op) mice have reduced microglia, no Aβ deposition, and no changes in dopaminergic neurons

<p>Abstract</p> <p>Background</p> <p>Activation of microglia is a part of the inflammatory response in neurodegenerative diseases but its role in the pathophysiology of these diseases is still unclear. The osteopetrotic (op/op) mouse lacks colony-stimulating factor-1 (CSF-1) and thus has a deficiency in microglia and macrophages. Prior reports have demonstrated that op/op mice deposit amyloid β (Aβ) plaques, similar to those found in Alzheimer's disease. The purpose of these studies was to confirm this and to determine if the lack of CSF-1 affects the development of dopaminergic neurons and the expression of CD200, a known microglial inhibitory protein.</p> <p>Method</p> <p>We examined the central nervous system of op/op mice at 30 days, 60 days and 7 months of age and wildtype littermates at 30 days using immunohistochemistry and histochemistry.</p> <p>Results</p> <p>We found a decrease in the number of microglia in 1 month-old op/op mice compared to wildtype (WT) littermates as measured by CD11b, CD45, CD32/16, CD68, CD204 and F4/80 immunoreactivity. Aβ plaques were not detected, while the number of dopaminergic neurons appeared normal. The expression of CD200 appeared to be normal, but there appeared to be a lower expression in the substantia nigra.</p> <p>Conclusion</p> <p>In contrast to a prior report we did not detect Aβ deposition in the central nervous system of op/op mice at 30 days, 60 days or 7 months of age and there was a normal number of dopaminergic neurons. This indicates that op/op mice may be useful to examine the effects of microglia on neurodegenerative disease progression by breeding them to different transgenic mouse models. In addition, the lack of CSF-1 does not appear to affect CD200 expression by neurons but we did note a decrease in the substantia nigra of op/op and WT mice, suggesting that this may be a mechanism by which microglia control may be attenuated in this specific area during Parkinson's disease.</p

Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma

Stimulation of adenosine receptor enhances α1 -adrenergic receptor-mediated activation of phospholipase C and Ca2+ mobilization in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells

AbstractNorepinephrine (NE) stimulated FRTL-5 thyroid cells via an α1-adrenergic receptor, resulting in cytosolic Ca2+ ([Ca2+]i) mobilization and activation of phospholipase C. Adenosine and its receptor agonist, phenylisopropyladenosine (PIA), although not exerting a direct effect, markedly enhanced the NE-induced changes. Basal NE action was not totally abolished whereas the permissive action of adenosine and PIA was completely abolished by pretreatment of the cells with islet-activating protein (IAP), pertussis toxin. The decrease in cAMP level induced by adenosine or PIA is not the cause of their permissive effect, since this effect was not reversed by the addition of cAMP-increasing agents. We conclude that an IAP substrate GTP-binding protein(s) plays a novel role in forming a stimulatory coupling between an adenosine receptor and an α1-adrenergic receptor-coupled phospholipase C system

Dance Generation by Sound Symbolic Words

This study introduces a novel approach to generate dance motions using onomatopoeia as input, with the aim of enhancing creativity and diversity in dance generation. Unlike text and music, onomatopoeia conveys rhythm and meaning through abstract word expressions without constraints on expression and without need for specialized knowledge. We adapt the AI Choreographer framework and employ the Sakamoto system, a feature extraction method for onomatopoeia focusing on phonemes and syllables. Additionally, we present a new dataset of 40 onomatopoeia-dance motion pairs collected through a user survey. Our results demonstrate that the proposed method enables more intuitive dance generation and can create dance motions using sound-symbolic words from a variety of languages, including those without onomatopoeia. This highlights the potential for diverse dance creation across different languages and cultures, accessible to a wider audience. Qualitative samples from our model can be found at: https://sites.google.com/view/onomatopoeia-dance/home/

Histological development of stapes footplate in human embryos.

Normal development of the human stapes footplate was investigated in serial sections by light microscopy. Materials were obtained from 35 Japanese embryos from the 6th to 32nd week of embryonal age. Eighteen embryos up to 16 weeks of age (3.5mm to 105mm in crown-rump length) were examined, focusing particularly on the lamina stapedialis of the otic capsule. The present study showed that primordial formation of the lamina stapedialis appeared in 16mm embryo and that the lamina was completely formed and fused to the base of the annular stapes in a 35mm embryo. In a 50mm embryo, the adult form of stapes was found with a rim and annular ligament. The results, therefore, seemed to essentially agree with the theory of dual origin and development of the footplate proposed by Cauldwell and Anson, and teratogenic agents might affect any stage of the process producing anomalies,</p

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

Background Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). Case presentation An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. Conclusions It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay

Abnormal Movements of Japanese Infants following Treatment with Midazolam in a Neonatal Intensive Care Unit: Incidence and Risk Factors

Background. This study was conducted to investigate the incidence of, and factors associated with, myoclonus-like abnormal movements of Japanese infants following treatment with midazolam in a neonatal intensive care unit (NICU). Methods. We retrospectively investigated abnormal movements and associated risk factors in Japanese infants (less than 1 year old) who received continuous intravenous midazolam treatment in the NICU of the Neonatal Medical Center, Kumamoto City Hospital, Japan, between April 2007 and March 2009. Results. The study included 94 infants who received 119 sessions of midazolam treatment in total. Nine infants (9.6%) developed abnormal movements attributable to midazolam. These nine patients had a significantly lower gestational age at birth, a significantly lower number of weeks after conception at the start of midazolam treatment, and significantly lower body weight compared with patients free of abnormal movements. Logistic regression analysis revealed neonatal asphyxia as a factor associated with an elevated risk of abnormal movements (P = 0.03). Conclusion. The incidence of abnormal movements after midazolam treatment was about 9.6% among the Japanese NICU infants. This result suggests that neonatal asphyxia may be involved in the onset of abnormal movements in infants treated with midazolam

Lactoferrin-like Immunoreactivity in Distinct Neuronal Populations in the Mouse Central Nervous System

Lactoferrin (Lf) is an iron-binding glycoprotein mainly found in exocrine secretions and the secondary granules of neutrophils. In the central nervous system (CNS), expression of the Lf protein has been reported in the lesions of some neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as in the aged brain. Lf is primarily considered an iron chelator, protecting cells from potentially toxic iron or iron-requiring microorganisms. Other biological functions of Lf include immunomodulation and transcriptional regulation. However, the roles of Lf in the CNS have yet to be fully clarified. In this study, we raised an antiserum against mouse Lf and investigated the immunohistochemical localization of Lf-like immunoreactivity (Lf-LI) throughout the CNS of adult mice. Lf-LI was found in some neuronal populations throughout the CNS. Intense labeling was found in neurons in the olfactory systems, hypothalamic nuclei, entorhinal cortex, and a variety of brainstem nuclei. This study provides detailed information on the Lf-LI distribution in the CNS, and the findings should promote further understanding of both the physiological and pathological significance of Lf in the CNS