ADC Level is Related to DWI Reversal in Patients Undergoing Mechanical Thrombectomy: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment. RESULTS: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10-6 mm2/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10-6 mm2/s. The mean ADC threshold was 520 × 10-6 mm2/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (P < .0001). CONCLUSIONS: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10-6 mm2/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.

A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484/protocadherin-19 signaling.

Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus-conserved across mice and humans-contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3'-untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome.

A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons.

Valproic acid (VPA) is a branched-chain saturated fatty acid with a long history of clinical use as an antiepileptic drug (AED). VPA is also known to inhibit histone deacetylases (HDACs) and to cause diverse effects on neural progenitor cells (NPCs) and neurons. Although the neuroprotective or neurodestructive effects of VPA have been investigated in heterogeneous cell populations, in this study, we used homogeneous populations of NPCs and glutamatergic cortical pyramidal neurons, which were differentiated from embryonic stem (ES) cells. At therapeutic concentrations, VPA had a proapoptotic effect on ES cell-derived NPCs of glutamatergic neurons, but not on their progeny. This effect of VPA most likely occurred through the inhibition of HDACs, because similar phenotypes were observed following treatment with other HDAC inhibitors (HDACis) such as trichostatin A and sodium butyrate. The proapoptotic phenotype was not observed when cells were exposed to a structural analog of VPA, valpromide (VPM), which has the same antiepileptic effect as VPA, but does not inhibit HDACs. Western blotting confirmed that treatment with HDACis, but not VPM, significantly increased the levels of histone H3 acetylation in NPCs. HDACi treatments did not affect the survival of neurons, although the acetylation levels were increased to a limited extent. These results, which are based on a homogeneous culture system, suggest that VPA inhibits HDAC activity and induces the apoptosis of NPCs that are fated to differentiate into glutamatergic neurons. The dose-dependent effects of VPA both on apoptosis and hyperacetylation of histone H3 in NPCs supported this notion. These cell type- and differentiation stage-specific effects of VPA imply that dysfunction of HDACs during pregnancy significantly increase the risk of congenital malformations associated with VPA administration.

Regulated histone methyltransferase and demethylase complexes in the control of genes by nuclear receptors.

Liganded nuclear receptors (NRs) are DNA-binding transcription factors that control the transcription of target genes. Such NRs exert their transcriptional functions via ligand binding-induced interactions with a number of coregulator complexes to reorganize chromatin state. Intensive investigation of NR coregulator complexes has revealed that, besides histone acetylation, histone methylation is critical for ligand-dependent transcriptional controls by NRs. Our recent biochemical screening for NR coregulator complexes showed that the enzymatic activities of these histone methylation/demethylation complexes are under the control of posttranslational modifications (PTMs) of their catalytic subunit. Characterization of such regulated complexes has established the concept that transcriptional coregulator complexes sense and decode cellular signals at the molecular level. In this symposium review, we will illustrate our recent findings regarding PTM-based regulation of NR transcriptional control and discuss how these findings are applicable to the diverse roles of NR coregulators in interpreting regulatory signals into proper gene regulation.

Phase I and pharmacokinetic study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer.

PURPOSE: A phase I study was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of carboplatin in combination with paclitaxel using a biweekly schedule in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The pharmacokinetics of paclitaxel were determined preliminarily in some patients. The criteria for eligibility for study entry included histologically and/or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable disease. Paclitaxel was given in combination with a fixed dose of carboplatin at an area under the concentration-time curve (AUC) of 3 mg/ml x min, every 2 weeks. The starting dose of paclitaxel was 100 mg/m(2), and the dose was increased in increments of 20 mg/m(2). Three to six patients were allocated to each dose level. RESULTS: A total of 19 patients (11 male and 8 female) with a median age of 61 years (range 43-74 years) and a median ECOG performance status of 0 (range 0-1) were enrolled. The MTD of paclitaxel proved to be 160 mg/m(2), and the DLT was neutropenia, which improved well following treatment with G-CSF. Gastrointestinal toxicity was well tolerated. Of 17 patients who received four cycles or more, 7 (41%; 95% confidence interval 18.4-67.1%) responded to this combination therapy. The pharmacokinetics of paclitaxel did not differ from published data. CONCLUSIONS: The recommended dose for phase II study is paclitaxel 140 mg/m(2) with a carboplatin AUC of 3 mg/ml.min. This biweekly regimen is highly effective and acceptable, and the present data indicate that the regimen may be suitable for use on an outpatient basis.

Clinical study of severe influenza virus pneumonia that caused acute respiratory failure.

The mortality of the influenza virus pneumonia is on the increase caused by the decline of the vaccination for the influenza virus in Japan. The purpose of our research is to study the clinical feature of severe influenza virus pneumonia that caused acute respiratory failure. This study included 68 patients with adult influenza virus infection who consulted our hospital between October 1997 and May 1999. Six (8.8%) of 68 were diagnosed as having influenza virus pneumonia that caused acute respiratory failure. All patients with influenza virus pneumonia showed severe conditions with respiratory failure and a high-risk group. Two super high age patients had emergency status with unconsciousness. A super high age patient with influenza virus pneumonia died of aspiration pneumonia 118 days after admission. All patients with influenza virus pneumonia were received antibiotics. Although 4 of 6 patients did not respond to antibiotics, adrenocorticosteroids were administered. As the result, 3 of 4 patients, healing was achieved. We concluded that adrenocorticosteroids might be useful for treating severe influenza virus pneumonia under the administration of appropriate antibiotics.

Malignant mesothelioma of the tunica vaginalis testis: report of a case.

We describe herein the case of a 68-year-old man with malignant mesothelioma of the tunica vaginalis testis. The pathological diagnosis was based upon the clinical findings, gross and microscopic morphology, and special stains. Malignant mesothelioma is a rare tumor associated with asbestos exposure that can be effectively treated with orchidectomy via an inguinal approach.

Isolation and structure of cytostatic steroidal saponins from the African medicinal plant Balanites aegyptica.

Bioactivity-guided separation of a CH2Cl2/MeOH extract of Balanites aegyptica afforded four new cytostatic saponins, named balanitins 4 [1], 5 [2], 6 [3], and 7 [4]. On the basis of enzymatic hydrolyses and glycosidation nmr chemical shifts employing the peracetates, structures 1-4 were established as yamogenin 3 beta-O-beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)-[al pha- L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [1], yamogenin 3 beta-O-alpha-L-rhamnopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)- [alpha-L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [2], yamogenin 3 beta-O-beta-D-glucopyranosyl-(1----4)-[alpha-L- rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [3], and diosgenin 3 beta-O-beta-D-xylopyranosyl-(1----3)-beta-D-glucopyranosyl-(1----4)-[alp ha- L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranoside [4].

Cytotoxic activity of marine algae and a cytotoxic principle of the brown alga Sargassum tortile.

Partition fractions of hexane, CCl4 and CHCl3 from methanolic extracts of marine algae were each examined for cytotoxic activities against cultured P-388 lymphocytic leukemia cells. Cytotoxic activities were found for partition fractions of 21 species of seaweed. Bioactivity-guided fractionation of the CCl4 partition fraction from Sargassum tortile, exhibiting the most prominent activity, afforded dihydroxysargaquinone (1) and sargatriol (2) previously isolated from this alga. The former was evaluated as a cytotoxic principle, and the latter, showing moderate activity, was suggested to be an artifact derived from 1 during the isolation procedure.

Plant constituents biologically active to insects. VI. Antifeedants for larvae of the yellow butterfly, Eurema hecabe mandarina, in Osmunda japonica. (2).

Three antifeedants for larvae of the yellow butterfly, Eurema hecabe mandarina de l'Orza, were isolated from Osmunda japonica Thunb. and identified as osmundalin, parasorboside and methyl (3S,5S)-5-hydroxy-3-(beta-D-glucopyranosyloxy)hexanoate. In the course of isolation of the antifeedants, a new glycoside, dihydroisoosmudalin (9), was isolated together with maltol beta-D-glucopyranoside, 2-deoxy-L-ribopyranolactone, 5-hydroxymethyl.2-furfural and glycerin. The structure of 9 was elucidated as (4R,5S)-5-(beta-D-glucopyranosyloxy)hexan-4-olide on the basis of chemical and spectroscopic evidence.

Cytotoxic triterpenes from a Chinese medicine, Goreishi.

Bioactivity-guided fractionation of the methanol extract of Goreishi (the feces of Trogopterus xanthipes Milne-Edwards) afforded one new and three known cytotoxic triterpenes, namely, 3-O-cis-p-coumaroyltormentic acid, pomolic acid, 2 alpha-hydroxyursolic acid, and jacoumaric acid. In the course of this investigation, six additional compounds having no cytotoxic activity were isolated, namely, maslinic acid, 3-O-trans-p-coumaroylmaslinic acid, ursolic acid, tormentic acid, euscaphic acid, and a new triterpene, 3-O-trans-p-coumaroyltormentic acid. The structures of the new compounds were established on the basis of X-nucleus-proton correlation with fixed evolution time (XCORFE) and other spectroscopic evidence.