Extremely slow-growing cerebellar ganglioglioma in an elderly patient.

Background: Gangliogliomas account for 0.4% of primary brain tumors. They mainly occur in the supratentorial compartment and typically affect only children and young adults.

Profiling of Unfolded Protein Response Markers and Effect of IRE1α-specific Inhibitor in Pituitary Neuroendocrine Tumor.

Context: Inositol-requiring enzyme 1α (IRE1α) and PKR-like ER kinase (PERK), which are endoplasmic reticulum (ER) membrane proteins, regulate the unfolded protein response (UPR). These molecules have recently gained attention as a novel therapeutic target in secretory tumors. The roles of the UPR in pituitary neuroendocrine tumors (PitNETs) are unclear.

Hemangioblastoma of the medulla oblongata that caused isolated fourth ventricle after stereotactic radiosurgery: A case report.

Isolated fourth ventricle is a rare complication following shunt insertion of the lateral ventricles for hydrocephalus. The present report describes a rare case of a hemangioblastoma of the medulla oblongata that caused isolated fourth ventricle due to intraventricular deposition of fibrin. A 34-year-old man presented with headache a month before admission.

Rituximab Monotherapy for Grade 2-3 Lymphomatoid Granulomatosis with Central Nervous System Involvement in a Patient Receiving Methotrexate for Rheumatoid Arthritis.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder (LPD). The optimal management strategy of methotrexate (MTX) related-LPD with central nervous system (CNS) involvement and histological features of LYG remains unclear. We herein report a case of grade 2-3 LYG in a rheumatoid arthritis patient, in which an intracranial mass accompanied by hemorrhaging and pulmonary and skin lesions developed.

Hemorrhagic brain metastasis from small-cell carcinoma of the urinary bladder.

Background: Small-cell carcinoma of the urinary bladder (SCCB) accounts for 1% of all bladder tumors. We present a rare case of hemorrhagic metastatic brain tumor from SCCB diagnosed by navigation-guided endoscopic biopsy.

Case Description: A 76-year-old man presented with sudden onset of aphasia and right hemiplegia from 3 weeks previously.

Three-dimensional morphology of the superior cerebellar artery running in trigeminal neuralgia.

The superior cerebellar artery (SCA) is the most frequent offending vessel in trigeminal neuralgia. This study aims to elucidate the patterns of the SCA running in 34 patients with typical trigeminal neuralgia using three-dimensional computer graphics. The SCA which runs in the medial aspect of the trigeminal nerve compressed predominantly the root entry zone at the distal segment of the caudal loop.

Biochemical profiles of rat primary cultured hepatocytes following treatment with rotenone, FCCP, or (+)-usnic acid.

The metabolomic profiles of rat primary hepatocytes following treatment with rotenone, FCCP, or (+)-usnic acid were determined using liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-mass spectrometry. Significant and similar changes in the levels of 283 biochemical metabolites were associated with the three treatments compared with solvent control samples. Overall, the three treatments generated similar global biochemical profiles, with some minor differences associated with rotenone treatment.

Aphasic status epilepticus of frontal origin treated by resective surgery.

Aphasic status epilepticus (SE) is a clinical entity of SE, but it has not been well recognized. We report a 43-year-old female with a chronic drug-resistant epilepsy with aphasic SE, treated by resective surgery. The patient showed long-lasting weekly episodes of hypokinesia, slow verbal response, and dysphasia, which were diagnosed as symptoms of aphasic SE.

Species differences in micronucleus induction of the clastogenic compounds associated with drug metabolic profile.

Genotoxicity and carcinogenicity profiles of drugs occasionally vary across species due to species difference in drug metabolic profile. To clarify the effect of species differences in the metabolic profile on micronucleus induction, we conducted an in vitro micronucleus test for seven clastogens (benzo[a]pyrene: BaP, cyclophosphamide monohydrate: CPA coumarin, diclofenac, piroxicam, lansoprazole, and chlorpheniramine) with rat, mouse, monkey, dog, or human liver S9. BaP, CPA, coumarin, diclofenac, piroxicam, and lansoprazole induced micronucleus formation with all species of S9s, whereas chlorpheniramine did not induce micronucleus formation in any of the S9s.

Effect of the metabolic capacity in rat liver S9 on the positive results of in vitro micronucleus tests.

A high incidence of positive results is obtained with in vitro genotoxicity tests, which do not correlate with the in vivo negative results in many cases. To address this issue, the metabolic profile of rat liver 9000 × g supernatant fraction (S9) pretreated with phenobarbital (PB) and 5,6-benzoflavone (BNF) was characterized. Furthermore, the in vitro micronucleus tests of 10 compounds were performed with PB-BNF-induced rat S9.

Effect of inter-individual variability in human liver cytochrome P450 isozymes on cyclophosphamide-induced micronucleus formation.

We investigated the relationship between metabolic activities of cytochrome P450 (CYP) isozymes present in microsomal fractions derived from the livers of 78 donors and micronucleus induction by cyclophosphamide (CPA). Consequently, a wide inter-individual variation in CYP activities was observed among the 78 donors. The CYP activities were partially correlated with the metabolic phenotypes predicted for the donors based on their single nucleotide polymorphisms.

Controlling the Emergence and Shift Direction of Mechanochromic Luminescence Color of a Pyridine-Terminated Compound.

In this study, mechanochromic luminescence was induced in a complex of mechano-inactive compounds. Dye/acid complexes containing the same π-conjugated backbones were prepared. While the luminophore showed blue and red shifts in photoluminescence spectra when combined with different acids by grinding, it exhibited slight mechanoresponsiveness itself.

Plasma 2-hydroxyglutarate, a promising prognostic biomarker candidate for skeletal muscle injury in Fischer 344 rats.

Previously, we have demonstrated the potential of plasma 2-hydroxyglutarate (2HG) as an easily detectable biomarker for skeletal muscle injury in rats. Here, we examined whether plasma 2HG was superior to conventional skeletal muscle damage biomarkers, including aspartate aminotransferase (AST), creatine kinase (CK), and skeletal muscle-type CK isoenzyme (CK-MM) levels, in rats. Skeletal muscle injury was induced in 4- or 9-week-old male Fischer 344 rats by cerivastatin (CER) or tetramethyl-p-phenylenediamine (TMPD) administration.

Plasma 2-hydroxyglutarate and hexanoylcarnitine levels are potential biomarkers for skeletal muscle toxicity in male Fischer 344 rats.

To identify new candidate biomarkers for skeletal muscle toxicity, an unbiased metabolomic analysis was performed in rats treated with two distinct myotoxicants, cerivastatin (CER) and tetramethyl-p-phenylenediamine (TMPD). Skeletal muscle toxicity was induced in male Fischer 344 rats by administering CER or TMPD and monitored using established endpoints, such as increased plasma creatine kinase (CK) activity and histopathology, and a metabolomic analysis of skeletal muscle and plasma samples. Plasma CK levels in CER-treated rats were markedly elevated at Day 11; however, those in TMPD-treated rats showed a statistically significant decrease at 24 hr after dosing.

Ruptured internal carotid artery aneurysm presenting with catastrophic epistaxis after repeated stereotactic radiotherapies for anterior skull base tumor: case reports and review of the literature.

Objectives Radiation-induced aneurysm is a rare complication for head and neck tumors. Only seven cases of an aneurysm after stereotactic radiosurgery and/or stereotactic radiotherapy (SRT) have been described. We report two patients with a ruptured internal carotid artery (ICA) aneurysm presenting with catastrophic epistaxis after repeated SRT for an anterior skull base tumor.

Intracranial extension of adenoid cystic carcinoma: potential involvement of EphA2 expression and epithelial-mesenchymal transition in tumor metastasis: a case report.

Background: Adenoid cystic carcinoma is a malignant epithelial tumor derived from salivary glands and tends to invade the surrounding structures including nervous system. We present a case of adenoid cystic carcinoma with intracranial extension and propose a novel molecular mechanism of adenoid cystic carcinoma metastasis.

Case Presentation: A 29-year-old Japanese male presented with left trigeminal nerve disturbance.

A case of orbital emphysema associated with frontal sinus pneumocele.

Orbital emphysema is usually caused by trauma and fracture of an orbital bone, allowing air to pass from the sinuses into the orbit. Orbital emphysema without any significant trauma is rare. We present a case of a 67-year-old-woman who complained of left exophthalmos without any history of trauma, sneezing, or sinus surgery.

A 1H NMR-based metabolomics approach for mechanistic insight into acetaminophen-induced hepatotoxicity.

The widely used analgesic-antipyretic drug acetaminophen (APAP) is known to cause serious liver necrosis at high doses in man and experimental animals. For studies of toxic processes, 1H NMR spectroscopy of biofluids allows monitoring of endogenous metabolite profiles that alter characteristically in response to changes in physiological status. Herein, a 1H NMR metabolomics approach was applied to the investigation of APAP toxicity in rats and the effect of phenobarbital (PB) on APAP-induced hepatotoxicity.

Hepatic transcriptome and proteome responses against diethyl maleate-induced glutathione depletion in the rat.

Hepatic transcriptome and proteome responses against glutathione depletion were investigated by Affymetrix GeneChip Microarray and 2-dimensional gel electrophoresis (2D-DIGE), followed by MALDI-TOF-MS analysis and utilizing a glutathione-depleted rat model treated with diethyl maleate (DEM). Hepatic glutathione content decreased to 1.29 μmol/g liver (25.

Relationship between DNA damage and micronucleus in mouse liver.

To determine the optimum timing of partial hepatectomy (PH) in a previously developed mouse liver micronucleus test (Igarashi and Shimada, 1997), the relation between DNA damage and micronucleus was examined using the in vivo alkaline comet assay and the micronucleus test on the liver of the same individual mouse. Five genotoxic carcinogens, 1-nitropyrene (1-NP) (125 mg/kg), cyclophosphamide (CP) (50 mg/kg), methylmethan sulfonate (MMS) (80 mg/kg), mitomycin C (MMC) (2 mg/kg) and diethylnitrosamine (DEN) (50 mg/kg) were intraperitoneally dosed to each group consisting of 4 male ddY mice. The mice were subjected to PH 3, 8 or 24 hr after dosing of each carcinogen, and comet assay was performed using the removed liver.

Practical application of toxicogenomics for profiling toxicant-induced biological perturbations.

A systems-level understanding of molecular perturbations is crucial for evaluating chemical-induced toxicity risks appropriately, and for this purpose comprehensive gene expression analysis or toxicogenomics investigation is highly advantageous. The recent accumulation of toxicity-associated gene sets (toxicogenomic biomarkers), enrichment in public or commercial large-scale microarray database and availability of open-source software resources facilitate our utilization of the toxicogenomic data. However, toxicologists, who are usually not experts in computational sciences, tend to be overwhelmed by the gigantic amount of data.

In vitro cytotoxicity assay to evaluate the toxicity of an electrophilic reactive metabolite using glutathione-depleted rat primary cultured hepatocytes.

Glutathione plays an important role as not only a scavenger of reactive oxygen species but also in the conjugation or detoxification of electrophilic reactive metabolites, which has been thought to be one of the causes for idiosyncratic drug toxicity (IDT). Therefore, toxic responses to the reactive metabolites have been expected to be expressed more strongly in a glutathione-depleted condition. In the present study, we attempted to establish an in vitro cytotoxicity assay method to evaluate the toxicity of the reactive metabolite using rat primary cultured hepatocytes with cellular glutathione depletion by l-buthionine-S,R-sulfoximine.

Ethylene glycol monomethyl ether-induced toxicity is mediated through the inhibition of flavoprotein dehydrogenase enzyme family.

Ethylene glycol monomethyl ether (EGME) is a widely used industrial solvent known to cause adverse effects to human and other mammals. Organs with high metabolism and rapid cell division, such as testes, are especially sensitive to its actions. In order to gain mechanistic understanding of EGME-induced toxicity, an untargeted metabolomic analysis was performed in rats.

Gene set-level network analysis using a toxicogenomics database.

Toxicogenomics data sets on rat livers covering 118 compounds were subjected to inference of a gene set-level, not individual gene-level, network structure. Expression changing levels for 58 gene sets was used for network inference with a Gaussian graphical model algorithm. The established network contained reasonable relationships, such as ones between the blood glucose level and glycolysis-related genes or the blood transaminase level and cellular injury-related genes, indicating that the gene set-level network inference successfully highlighted biological pathway-level interactions.

Comprehensive analysis of hepatic gene and protein expression profiles on phenobarbital- or clofibrate-induced hepatic hypertrophy in dogs.

In order to characterize the hepatic effects of phenobarbital (PB) and clofibrate (CPIB) in dogs, PB and CPIB were administered to male beagle dogs for 14 days, and biochemical and histopathological examinations and comprehensive genomic and proteomic analyses, including GeneChip analysis and proteomics analysis using the 2-dimension difference gel electrophoresis (2D-DIGE) technique, were performed. Both compounds caused centrilobular hepatocellular hypertrophy, which were related to smooth endoplasmic reticulum (SER) proliferation in PB-treated dogs and to mitochondrial proliferation in CPIB-treated dogs. In the PB-treated dogs, drug-metabolizing enzyme induction was observed by Western blot and genomic analyses.