Cyclic AMP levels in slices of epileptic cortex of the rat: effects of glutamate and 3-isobutyl-1-methylxanthine.

Accumulation of cyclic AMP elicited by glutamate was examined in slices from different cortical areas of rats 30 to 60 days after ferrous chloride solution was injected into the left sensorimotor cortex to induce an epileptic focus. In the anterior cortex of rats showing dominant electrographic spike activity on either side of the cortex, the glutamate-elicited accumulation of cyclic AMP was greater on the dominant side than on the other. In the anterior cortex of rats showing nearly equal spike activity on either side, the accumulation was greater on the side ipsilateral to the injection site than on the other. Different inhibitory effects of 3-isobutyl-1-methylxanthine on the elicitation of cyclic AMP accumulation by glutamate was observed in relation to the patterns of spike activity.</p

Effects of prolonged weak anodal direct current on electrocorticogram in awake rabbit.

The effects of prolonged weak anodal direct current (DC) on the electrocorticogram (ECoG) were investigated in awake rabbits. When the current (20-40 microA) was applied to the motor region of the cerebral cortex, seizure activity in the ECoG appeared from the frontal cortex. Repeated application of the DC decreased the threshold current for producing the seizure activity. Diazepam significantly elevated the threshold of the seizure activity. In contrast to the marked changes in the ECoG, no behavioral changes were observed during or after the application of weak anodal DC. The changes in the ECoG are discussed in relation to the intensity and duration of the DC.</p

Embedded Ubiquitous Services on Hospital Information Systems.

A Hospital Information Systems (HIS) have turned a hospital into a gigantic computer with huge computational power, huge storage and wired/wireless local area network. On the other hand, a modern medical device, such as echograph, is a computer system with several functional units connected by an internal network named a bus. Therefore, we can embed such a medical device into the HIS by simply replacing the bus with the local area network. This paper designed and developed two embedded systems, a ubiquitous echograph system and a networked digital camera. Evaluations of the developed systems clearly show that the proposed approach, embedding existing clinical systems into HIS, drastically changes productivity in the clinical field. Once a clinical system becomes a pluggable unit for a gigantic computer system, HIS, the combination of multiple embedded systems with application software designed under deep consideration about clinical processes may lead to the emergence of disruptive innovation in the clinical field

Repeated application of anodal direct current produces regional dominance in histamine-elicited cyclic AMP accumulation in rabbit cerebral cortex.

A unilateral 30-min application of anodal direct current to the promotor cortex of rabbits was repeated 10 times, and cyclic AMP accumulation in response to histamine was investigated in slices of different cortical areas. Polarization with 1.0 microA decreased the cyclic AMP accumulation in the cortical area contralateral to the polarization, by which regional dominance in cyclic AMP accumulation was produced in the polarized cortex. In contrast, the regional difference in cyclic AMP accumulation was reversed when 10.0 or 30.0 microA was applied. The histamine-elicited accumulation of cyclic AMP was almost completely inhibited by the selective H2-receptor antagonist cimetidine. These results suggest that repeated anodal polarization regionally alters H2-receptor-mediated cyclic AMP generation in the cortex depending on the intensity of the polarizing currents and this pattern of cyclic AMP accumulation is responsible for the characteristic motor behavior induced by anodal polarization.</p

Overexpression of the human MNB/DYRK1A gene induces formation of multinucleate cells through overduplication of the centrosome

BACKGROUND: Previously we cloned the human MNB/DYRK1A gene from the "Down syndrome critical region" on chromosome 21. This gene encodes a dual specificity protein kinase that catalyzes its autophosphorylation on serine/threonine and tyrosine residues. But, the functions of the MNB/DYRK1A gene in cellular processes are unknown. RESULTS: In this study, we examined HeLa cells transfected with cDNA encoding a green fluorescent protein (GFP)-MNB/DYRK1A fusion protein and found 2 patterns of expression: In one group of transfected cells, GFP-MNB/DYRK1A was localized as dots within the nucleus; and in the other group, it was overexpressed and had accumulated all over the nucleus. In the cells overexpressing GFP-MNB/DYRK1A, multinucleation was clearly observed; whereas in those with the nuclear dots, such aberrant nuclei were not found. Furthermore, in the latter cells, essential processes such as mitosis and cytokinesis occurred normally. Multinucleation was dependent on the kinase activity of MNB/DYRK1A, because it was not observed in cells overexpressing kinase activity-negative mutants, GFP-MNB/DYRK1A (K179R) and GFP-MNB/DYRK1A (Y310F/Y312F). Immunostaining of GFP-MNB/DYRK1A-overexpressing cells with specific antibodies against α- and γ-tubulin revealed that multiple copies of centrosomes and aberrant multipolar spindles were generated in these cells. CONCLUSIONS: These results indicate that overexpression of MNB/DYRK1A induces multinucleation in HeLa cells through overduplication of the centrosome during interphase and production of aberrant spindles and missegregation of chromosomes during mitosis

N-ブチル-N-（4-ヒドロキシブチル）ニトロソアミン誘発膀胱癌マウスモデルを用いた膀胱内化学療法による局所及び全身の免疫応答

Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.博士（医学）・甲第695号・平成31年3月15日Copyright: © 2017 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Dual Effects of Cortical Polarization on Peripheral Motor Activity in the Rabbit

Anodal direct currents at intensities ranging from 0.3 to 30.0 microA were unilaterally applied for 30 min once a day to the premotor area of the rabbit cerebral cortex. The anodal polarization was repeated 10 times at intervals of 2-3 days, and the effect on the motor activity of the forelimbs during and after each polarization trial was compared with that before polarization. Peripheral motor activity was classified as either gentle flexion of forelimbs or struggle with violent movement of forelimbs. A current of 0.3 microA caused no change in motor behavior. Flexion of the forelimb contralateral to the polarized cortex was clearly increased when a polarizing current of 1.0 or 3.0 microA was applied, and peak flexion was observed between the third and seventh polarization trials. A current of 10 or 30 microA had no effect on forelimb flexion. Conversely, forelimb struggle on both sides was decreased when 10.0 or 30.0 microA, but not 1.0 or 3.0 microA, was applied. These results show that anodal polarization of the cerebral cortex exerts dual effects on peripheral motor activity, probably through changes in cortical excitability associated with the current intensity.</p

The role of the corpus callosum in interhemispheric propagation of iron-induced epileptogenic activity in the rat.

In iron-induced epilepsy, partial section of the corpus callosum resulted in a decrease in rats showing dominant spike activity on the side of secondary focus and an increase in rats showing almost equal spike activity on the sides of primary and secondary focus in electrocorticograms (ECoGs). Changes in ECoG spike frequencies caused by sectioning the corpus callosum included an increase in unilateral spikes on the side of primary focus, a decrease in unilateral spikes on the side of secondary focus, and an increase in bilateral spikes appearing almost synchronously on both sides.</p

Life sciences

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes.博士（医学）・甲第857号・令和4年12月22日Copyright © 2022 Elsevier Inc. All rights reserved

ラット膀胱での水吸収におけるアクアポリン-2の役割

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.博士（医学）・甲第697号・平成31年3月15日© 2018 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions