Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition.

Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions.

Regulation of Adult Mammalian Neural Stem Cells and Neurogenesis by Cell Extrinsic and Intrinsic Factors.

Tissue-specific stem cells give rise to new functional cells to maintain tissue homeostasis and restore damaged tissue after injury. To ensure proper brain functions in the adult brain, neural stem cells (NSCs) continuously generate newborn neurons that integrate into pre-existing neuronal networks. Proliferation, as well as neurogenesis of NSCs, are exquisitely controlled by extrinsic and intrinsic factors, and their underlying mechanisms have been extensively studied with the goal of enhancing the neurogenic capacity of NSCs for regenerative medicine.

Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain.

Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood.

Kinetic differentiation mode chromatography using 8-quinolinol and fluorimetric detection for sensitive determination of aluminum adhering to the gastric mucosa.

A highly sensitive method of kinetic differentiation (KD) mode high-performance liquid chromatography (HPLC) with fluorimetric detection was established using 8-quinolinol to measure aluminum adhering to the gastric mucosa. After sucralfate was hydrolyzed by 1 mol/l hydrochloric acid, an 8-quinolinolate-aluminum complex was produced by reacting aluminum with an 8-quinolinol solution. Then contaminants in the gastric mucosa and sucralfate were removed by liquid-liquid extraction with chloroform.

Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction.

We have previously isolated a lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal agent, by affinity chromatography on a CNBr-activated Sepharose 4B bound TS-2 monoclonal antibody (mAb) that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. In the current study, we compared the cytokine-inducing and anti-tumor activities of OK-PSA, a TS-2-binding fraction, with those of OK-PTF, a TS-2-unbinding fraction, in order to determine the efficacy of OK-PSA for clinical use in affinity chromatography using TS-2. In the in vitro experiments using human peripheral blood mononuclear cells (PBMCs), OK-PSA markedly induced Th1-type cytokines, while interleukin (IL)-6 and IL-10, Th2-type cytokines, were induced by OK-PTF.

Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432.

Background: The streptococcal agent OK-432 has been used for immunotherapy of head and neck cancer, among other malignancies, but its mechanism of action is unknown. Because the Toll-like receptor 4 (TLR4)/MD-2 complex is important in enabling the mammalian immune system to recognize bacterial components, we investigated whether expression of the TLR4 and MD-2 genes is associated with OK-432-induced anticancer immunity.

Methods: Peripheral blood mononuclear cells (PBMCs) from 28 patients with head and neck cancer were analyzed for TLR4 and MD-2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis.

Enhancement of anti-tumor immunity by lipoteichoic acid-related molecule isolated from OK-432, a streptococcal agent, in athymic nude mice bearing human salivary adenocarcinoma: role of natural killer cells.

Background: OK-PSA, a lipoteichoic acid (LTA)-related molecule isolated from a streptococcal agent OK-432, enhances anti-tumor immunity as a potent inducer of Th1-type cytokines. Recently, we obtained the data suggesting that natural killer (NK) cells may play a significant role for OK-PSA-induced cytokine production in vitro.

Materials And Methods: We conducted the animal experiments using athymic nude mice bearing human salivary adenocarcinoma to examine the role of NK cells in OK-PSA-induced anti-tumor immunity.