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Cerebellar outputs originate from the dentate nucleus (DN), project to the primary motor cortex (M1) via the motor thalamus, control M1 activity, and play an essential role in coordinated movements. However, it is unclear when and how the cerebellar outputs contribute to M1 activity. To address this question, we examined the response of M1 neurons to electrical stimulation of the DN and M1 activity during performance of arm-reaching tasks. Based on response patterns to DN stimulation, M1 neurons were classified into facilitation-, suppression-, and no-response-types. During tasks, not only facilitation- and suppression-type M1 neurons, but also no response-type M1 neurons increased or decreased their firing rates in relation to arm reaching movements. However, the firing rates of facilitation- and suppression-type neurons were higher than those of no-response-type neurons during both inter-trial intervals and arm reaching movements. These results imply that cerebellar outputs contribute to both spontaneous and movement-related activity in the M1, which help to maintain muscle tones and execute coordinated movements, although other inputs also contribute to movement-related activity. Pharmacological inactivation of the DN supports this notion, in that DN inactivation reduced both spontaneous firing rates and movement-related activity in the M1., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Background: Occipital sinus (OS) dural arteriovenous fistula (DAVF) is extremely rare, and we are aware of no case accompanied by cerebral hemorrhage. We present a case of OS DAVF presenting with cerebellar hemorrhage, treated successfully by transvenous embolization., Case Description: A 62-year-old female presented with headache and nausea of recent onset. Computed tomography revealed left cerebellar hemorrhage with perihematomal edema. Angiography showed OS DAVF fed by bilateral occipital and posterior meningeal arteries, with drainage into the left inferior hemispheric vein and right transverse sinus receiving the shunt flow from OS. The caudal side of the OS was occluded. The inferior hemispheric vein was dilated with 2 varices, and the junction between the OS and right transverse sinus was narrowed. Because the OS was not involved in normal cerebellar drainage, transvenous embolization of the OS was performed. The microcatheter was advanced to the OS from the transverse sinus during balloon occlusion at the confluence of sinuses. Coils were placed in the OS from the caudal to cranial side, and complete occlusion of the shunt was obtained., Conclusions: This is the first report of OS DAVF presenting with cerebellar hemorrhage. Transvenous embolization of the affected OS appears ideal when transvenous access is feasible, and the OS is not involved in normal venous drainage of the cerebellum., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Some mechanical thrombectomy techniques for acute ischemic stroke use a combination of an aspiration catheter and stent retriever. We experienced a rare case of aspiration catheter coil breakage and subsequent retrieval using a stent retriever., Case Description: A 79-year-old man suddenly developed somnolence, global aphasia, and right hemiplegia. Magnetic resonance imaging revealed acute infarction of the left frontal lobe and occlusion of the left common carotid artery. Thus, using an aspiration catheter and a stent retriever, mechanical thrombectomy was performed. The stent retriever was deployed from the middle cerebral artery to the internal carotid artery and retracted into the aspiration catheter placed in the internal carotid artery proximal to the thrombus. The catheter was bent during retraction of the stent retriever. After thrombus aspiration, the internal carotid and anterior and middle cerebral arteries were successfully reperfused; however, the stent retriever captured a broken section of the winding coil of the aspiration catheter. We suspected that an X-ray marker on the stent retriever broke the winding coil at the bent segment of the aspiration catheter and the stent captured the broken coil., Conclusions: The combined use of an aspiration catheter and a stent retriever may cause unexpected device breakage, especially when the catheter is bent., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rett syndrome (RTT) is a neurodevelopmental disorder mostly caused by mutations in Methyl-CpG-binding protein 2 (MECP2); however, mutations in various other genes may lead to RTT-like phenotypes. Here, we report the first case of a Japanese girl with RTT caused by a novel syntaxin-binding protein 1 (STXBP1) frameshift mutation (c.60delG, p.Lys21Argfs*16). She showed epilepsy at one year of age, regression of acquired psychomotor abilities thereafter, and exhibited stereotypic hand and limb movements at 3 years of age. Her epilepsy onset was earlier than is typical for RTT patients. However, she fully met the 2010 diagnostic criteria of typical RTT. STXBP1 mutations cause early infantile epileptic encephalopathy (EIEE), various intractable epilepsies, and neurodevelopmental disorders. However, the case described here presented a unique clinical presentation of typical RTT without EIEE and a novel STXBP1 mutation., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: The preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients., Methods: We retrospectively evaluated 154 consecutive gastric cancer patients. We compared the perioperative outcomes and median survival times (MSTs). In particular, for stage II/III (UICC, 7th edition) gastric cancer patients, we compared median disease-free survival time (MDFST) between the low- and high-NLR groups., Results: Between the low-NLR group (n = 110) and the high-NLR group (n = 44), significant differences were observed in perioperative outcomes, including postoperative complications (3 (2.7%) vs. 5 (11.3%); p = 0.015), intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusions (0 vs. 3 (6.8%); p = 0.042). MSTs and MDFSTs were also significantly different (812 vs. 594 days, p = 0.04; and 848 vs. 475 days, p = 0.03, respectively). Multivariate analysis identified the NLR (hazard ratio [HR], 2.015; p = 0.004), Glasgow Prognostic Score (GPS) (HR, 1.533; p = 0.012), and presence of stage III/IV disease (HR, 5.488; p < 0.001), preoperative symptoms (HR, 3.412; p = 0.008), or postoperative complications (HR, 2.698; p < 0.001) as independent prognostic factors., Conclusions: We suggest that the preoperative NLR is an additional useful predictor of both long-term and short-term outcomes in gastric cancer patients., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To determine the morphological characteristics and pathogenic factors of cerebellar injury in extremely low birth weight infants (ELBWI)., Subjects and Methods: Neuroimaging examination was performed on 17 eligible surviving ELBWI. Their MR images were assessed and classified its pattern of cerebellar injuries. Brain pathology was examined on 15 patients, who isolated this neuroimaging subjects. The trend of brain pathologies was revealed., Results: Four types of morphological pattern were recognized: (i) the absence of major portions in the cerebellum (6/17 cases); (ii) focal cerebellar tissue loss (2/17); (iii) unilateral cerebellar atrophy/hypoplasia (3/17); (iv) small cerebellum with entrapped fourth ventricle (6/17). In cerebellar pathology, the most common findings were focal or widespread cerebellar subarachnoid hemorrhage (12/15) and olivocerebellar degeneration (12/15). In addition, one-third of the cases indicated remote cerebellar parenchymal hemorrhage., Conclusion: In MRI-defined lesions, the absence of major portions or focal tissue loss was associated with cerebellar parenchymal hemorrhage and/or hemorrhagic infarction, that is destructive lesion. On the other hand, small cerebellum or unilateral atrophy/hypoplasia, that is impaired development, may be related to the cerebellar neuron loss due to hemosiderin deposits in the surface of the cerebellum. The cerebellar injury in ELBWI is probably caused by not only environmental factors such as hemorrhage, hypoxia-ischemia, or other deleterious effect, but also immaturity of the rapidly growing cerebellum in particular gestational age., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones. Some of these findings overlapped to that of the patients with 16p13.11 microduplications and CFC syndrome. Although craniosynostosis was occasionally observed in patients with dominant-negative mutations in RAS/MAP kinase signaling genes (RASopathies) related to CFC syndrome, it was also reported in two patients with 16p13.11 microduplications. Genetic contributions of both chromosomal aberrations were discussed., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Prediction of motor function after intracerebral hemorrhage (ICH) often poses a diagnostic challenge. This study was performed to investigate whether intraoperative monitoring of motor-evoked potentials (MEPs) could predict postoperative motor function recovery., Methods: We reviewed 16 consecutive patients undergoing evacuation of supratentorial ICH with hemiplegia between June 2011 and October 2014. Patients were categorized according to the results of MEPs before and after evacuation of hematoma. The correlation between detection of MEPs and prognosis of motor function was analyzed., Results: In 10 of 16 cases (62%), stable MEPs were detected before and after evacuation of hematoma, and postoperative motor function was improved in all cases, including 3 cases with severe preoperative motor impairment on manual muscle test (1-2). In 3 cases (19%) in which MEPs were not detected throughout the procedure, motor function was not improved. In the other 3 cases (19%), MEPs were not measured before evacuation of ICH but were detected after evacuation despite poor prognosis of motor function. The results of postevacuation MEPs were considered false-negative results. Predictions using pre-evacuation MEP results were completely consistent with prognosis for recovery, whereas MEPs obtained during and after evaluation were useful for monitoring., Conclusions: Intraoperative MEPs may indicate preservation of pyramidal tracts, and pre-evacuation MEPs can predict motor function outcome after ICH surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We attempted to establish animal models to evaluate the effects of drug degradation in the stomach on oral bioavailability. In addition, we assessed the utilization of animal studies in determining the need for enteric-coated formulations. In order to control the gastric pH in rats and dogs, appropriate dosing conditions were investigated using pentagastrin and rabeprazole, which stimulate and inhibit gastric acid secretion. Using animals controlled for gastric acid secretion, the area under curve (AUC) ratios (AUC with rabeprazole/AUC with pentagastrin) of all compounds unstable under acidic conditions were evaluated. The AUC ratios of omeprazole and erythromycin, which are administered orally to humans, as enteric-coated tablets, were greater than 1.9 in the rats and dogs controlled for gastric acid secretion. On the contrary, the AUC ratios of clarithromycin, azithromycin, and etoposide (commercially available as a standard immediate-release form) were less than 1.3 each. In conclusion, in vivo models using rats and dogs were optimized to evaluate the effects of gastric acid on the oral bioavailability of drugs, and demonstrated that in vivo models can lead to a better understanding of the oral bioavailability, with respect to the formulation development., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Objective: This study aimed to elucidate the relationships between preoperative carotid imaging results, histologic characteristics, and surgical treatment outcomes of radiation-induced carotid stenosis (RICS), using control subjects without RICS for comparison., Methods: We retrospectively reviewed records of 17 patients who underwent carotid revascularization for 22 instances of RICS, including 10 cases of carotid artery stenting (CAS), 11 cases of carotid endarterectomy (CEA), and 1 case of CEA with retrograde CAS, between July 2004 and April 2013. The controls were 475 patients with no history of radiation therapy who underwent carotid revascularization in a similar period. Preoperative magnetic resonance imaging (MRI), ultrasonography (US), and computed tomography angiography results were correlated with outcomes of histologic analysis of CEA specimens. End points included ipsilateral and contralateral stroke, myocardial infarction, restenosis, in-stent thrombosis, and target lesion revascularization., Results: Vulnerable plaques on carotid MRI (86% vs 64.2%; P = .010) and mobile (27% vs 8.0%; P = .008) and ulcerative (50% vs 15.8%; P < .001) plaques on US were more frequent in the RICS group. All revascularization procedures were successful, and no occlusion occurred. Adverse events in the CAS group, including one minor stroke and one transient ischemic attack within 30 days as well as five ipsilateral neurologic events after 30 days, including three minor strokes and two transient ischemic attacks, were significantly more frequent than in the CEA group. All three cases of late ipsilateral stroke displayed vulnerable plaque on preoperative MRI and late in-stent thrombosis or restenosis on US., Conclusions: Our radiologic and histologic analyses revealed that advanced RICS is often accompanied by formation of vulnerable plaque. CEA can prevent undesirable late outcomes in such cases., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The characterisation of nanoscale surface properties of textile and hair fibres is key to developing new effective laundry and hair care products. Here, we develop nanomechanical methods to characterise fibres using an atomic force microscope (AFM) to give their nanoscale modulus. Good mounting methods for the fibre that are chemically inert, clean and give strong mechanical coupling to a substrate are important and here we detail two methods to do this. We show, for elastic nanoindentation measurements, the situation when the tip radius significantly affects the result via a function of the ratio of the radii of the tip and fibre and indicate the importance of using an AFM for such work. A valid method to measure the nanoscale modulus of fibres using AFM is thus detailed and exampled on hair to show that bleaching changes the nanoscale reduced modulus at the outer surface., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

Performance of metal catalysts to decompose aqueous phenol was experimentally investigated. Comparison of the phenol decomposition rates within three-phase fluidized-bed reactors utilizing only O(3), TiO(2) deposited on silica beads, metal catalyst (Ni or Co) impregnated on mesoporous carbon beads, or O(3) in combination with each catalyst was thoroughly examined. It was found that the use of Co catalyst with the presence of O(3) led to the best removal condition which aqueous phenol was completely decomposed within 10 min (k = 0.1944 min(-1)). In contrast, the use of TiO(2) without O(3) resulted in the worst decomposition of phenol (k = 0.0066 min(-1)). Some intermediate products, such as hydroquinone and catechol, were also detected but their final concentrations were negligibly low., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to develop a novel polymerase chain reaction (PCR) method to comprehensively analyze salivary bacterial flora., Study Design: The bacterial flora in the saliva of 10 healthy persons and 11 patients with odontogenic infections were examined using a DNA extraction method with a high level of cell destruction efficiency and a novel universal primer set to amplify approximately 580 bp of the 16S rDNA sequence., Results: Streptococcus (54.5%), Neisseria (14.7%), Actinomyces (8.4%), Gemella (4.1%), Granulicatella (3.8%), and Prevotella (1.4%) were dominant in a total of 1655 clones examined from the saliva of the healthy subjects. The dominant genera differed among the patients with odontogenic infections (a total of 823 clones) and were entirely different from those of the healthy subjects., Conclusion: This novel comprehensive salivary bacterial flora analysis method may be a useful supportive method to identify causative agents of odontogenic infections., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

We report herein of a 6-year-old boy with descending necrotizing mediastinitis (DNM) secondary to retropharyngeal abscess, who was successfully treated by the administration of antibiotics. DNM is very rare in children, and surgical drainage of the mediastinum is recommended in adult patients. DNM should be recognized as a severe complication of an oropharyngeal infection in children, and early and accurate diagnosis is important in ensuring appropriate clinical management.

Chromodomains are methylated histone binding modules that have been widely studied. Interestingly, some chromodomains are reported to bind to RNA and/or DNA, although the molecular basis of their RNA/DNA interactions has not been solved. Here we propose a novel binding mode for chromodomain-RNA interactions. Essential Sas-related acetyltransferase 1 (Esa1) contains a presumed chromodomain in addition to a histone acetyltransferase domain. We initially determined the solution structure of the Esa1 presumed chromodomain and showed it to consist of a well-folded structure containing a five-stranded beta-barrel similar to the tudor domain rather than the canonical chromodomain. Furthermore, the domain showed no RNA/DNA binding ability. Because the N-terminus of the protein forms a helical turn, we prepared an N-terminally extended construct, which we surprisingly found to bind to poly(U) and to be critical for in vivo function. This extended protein contains an additional beta-sheet that acts as a knot for the tudor domain and binds to oligo(U) and oligo(C) with greater affinity compared with other oligo-RNAs and DNAs examined thus far. The knot does not cause a global change in the core structure but induces a well-defined loop in the tudor domain itself, which is responsible for RNA binding. We made 47 point mutants in an esa1 mutant gene in yeast in which amino acids of the Esa1 knotted tudor domain were substituted to alanine residues and their functional abilities were examined. Interestingly, the knotted tudor domain mutations that were lethal to the yeast lost poly(U) binding ability. Amino acids that are related to RNA interaction sites, as revealed by both NMR and affinity binding experiments, are found to be important in vivo. These findings are the first demonstration of how the novel structure of the knotted tudor domain impacts on RNA binding and how this influences in vivo function.

Prominent dysphagia is seen among patients with spinal muscular atrophy (SMA) type 2, especially at the late stage of their disease progression. Nasogastric tube feeding and gastrostomy are commonly utilized to maintain their nutritional status. However, choosing a treatment strategy to maintain appropriate nutritional status is often complicated by multiple factors, such as physical conditions and social aspects. We report a 21-year-old man with SMA type 2 who has been suffering from severe dysphagia. The findings at video-fluoroscopic swallow study (VSS) were consistent with a diagnosis of cricopharyngeal dysphagia. His dysphagia was successfully treated with percutaneous injection of botulinum toxin A (BTA) into the cricopharyngeal muscle. Our result demonstrates that administration of BTA is one of the effective treatment choices for dysphagia in SMA patients.

Background: To understand what happens during the wound healing process of the mesothelium, we have developed an in vitro wounding model of cultured human peritoneal mesothelial cells (HPMCs) utilizing an image acquisition and analysis system. Using this system, cell mobility and hyaluronan synthesis were quantified and their interrelationship discussed., Methods: 1N NaOH was used to create circular wounds in cultured HPMC monolayers, which were then exposed for 30 minutes to the peritoneal dialysis solutions or fetal calf serum (FCS)-free M199 culture medium, followed by incubation with 0.3% FCS/M199 culture medium for up to 96 hours. Digitalized microscopic date was captured every 30 minutes to quantify the wound healing process. In separate experiments, the HPMC monolayers were stained with biotin-conjugated hyaluronan-binding protein (B-HABP) at a regular time interval., Results: Centripetal migration of the HPMCs into the wound area was the predominant process involved in wound repair with proliferation playing a secondary role. Two noticeable observations were made from the digital video movies: (1) cell mobility varied and was dependent upon the morphology and location of the cell relative to the wound edge, and (2) cell migration continued even after wound closure. Staining for B-HABP was confined to the remesothelialized area when wound closure was complete at 24 hours. At 48 hours after wound closure, the stained area was even more visible, although somewhat diffuse; thereafter, staining was reduced to almost background levels., Conclusion: The cell culture model of wound healing used in our study has enabled us to demonstrate quantitative image data of the cellular processes that occur during wound healing. We have been able to continuously observe cell migration, proliferation, and transformation. Synthesis and subsequent decomposition of hyaluronan appears to be related to the mobility of the wounded and intact HPMCs in this model system.

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transport has been suggested. Ursodeoxycholic acid, the 7beta-epimer of chenodeoxycholic acid, is clinically used for various hepatobiliary diseases. In our previous study, the contribution of multidrug resistance protein 2 for biliary excretion of taurine-conjugated bile acid sulfates depended on the numbers of hydroxyl residue. Therefore, to further examine the effect of hydrophobicity on the substrate specificity of multidrug resistance protein 2, we examined the effect of bile acid conjugates and organic anions on biliary excretion of tauroursodeoxycholate-3-sulfate, taurine and sulfonate-conjugated ursodeoxycholic acid, in rats. Biliary tauroursodeoxycholate-3-sulfate excretions was markedly delayed in Eisai hyperbilirubinemic rats. Taurolithocholate-3-sulfate inhibited but ursodeoxycholate-3,7-disulfate did not affect biliary tauroursodeoxycholate-3-sulfate excretion. Biliary tauroursodeoxycholate-3-sulfate excretion was inhibited by sulfobromophthalein, but was not inhibited by dibromosulfophthalein and cefpiramide. These findings indicate that tauroursodeoxycholate-3-sulfate is very specific for multidrug resistance protein 2.

Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1,6- and 3,6-dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo[a]BP (BP), are present in the environment. These derivatives are potent mutagens for Salmonella tester strains and we have preliminarily reported them to be carcinogenic in F344/DuCrj rats. In this study, the tumorigenic action of 1- and 3-NBP, 1.6- and 3,6-DNBP, and BP induced by subcutaneous injection into rats was found to differ according to the NO2-substitution in the BP structure. The chemicals were suspended in equal volumes of beeswax and tricaprylin, and rats were subcutaneously injected with single doses of 500, 1000, and 2000 microg for 1- and 3-NBP, and of 8, 40, 200, and 1000 microg for 3,6- and 1,6-DNBP, and BP as a positive control. 3,6-DNBP and BP induced tumors in a dose-dependent manner at the injection site. Rats given 1000 microg of 3,6-DNBP (2924 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate of 70 and 80%, respectively, and those given a minimum dose of 23 nmol for 3.6-DNBP and 32 nmol for BP per rat developed tumors at a rate of 4.8 and 18.2%, respectively. However, rats given 500 and 1000 microg of 1- and 3-NBP did not develop any tumors while those given a high dose, 2000 microg, of each chemical developed tumors at only one of ten animals used. It was concluded, therefore, that these chemicals are weak carcinogens. Histologically, most of the tumors were malignant fibrous histiocytomas. Rats given various doses of 1,6-DNBP did not develop any tumors at the injection site. The failure of 1,6-DNBP to induce tumors may involve its metabolites because of the lower mutagenicity of its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is suggested, therefore, that tumorigenicities of NBPs and DNBPs differ according to the NO2-substitution on the chemical structure, which may be due to the possible nitroreduction of the chemicals.

Background/aims: It has been suggested that vesicular transport of bile acids in hepatocytes occurs, especially at high-dose loads., Methods: The effect was studied of colchicine, a vesicular transport inhibitor, on lithocholate-3-O-glucuronide-induced cholestasis in rats. Cholestasis was induced by an intravenous infusion of lithocholate-3-O-glucoronide at the rate of 0.1 mumol.min-1.100 g-1 for 40 min., Results: Colchicine treatment almost completely inhibited cholestasis and increased biliary excretion of lithocholate-3-O-glucoronide, whereas lumicolchicine had no effect. Treatment with vinblastine, another vesicular transport inhibitor, also reduced the cholestasis. Colchicine did not affect biliary excretion of taurocholate infused at the rate of 0.3 mumol.min-1.100 g-1 for 40 min, but markedly inhibited its biliary excretion when infused at the rate of 1.5 mumol.min-1.100 g-1 for 40 min. Colchicine had no effect on biliary excretion of tauroursodeoxycholate (1.5 mumol.min-1.100 g-1 for 40 min), lithocholate-3-sulfate (0.3 mumol.min-1.100 g-1 for 40 min), or a trace amount of lithocholate-3-O-glucuronide., Conclusions: These findings indicate that lithocholate-3-O-glucoronide-induced cholestasis is caused by its increased access to the vesicular transport pathway, possibly beyond the capacity of the transport by the cytosolic binders, and that the transport of lithocholate-3-O-glucoronide via the vesicular pathway induces cholestasis. Furthermore, the contribution of the vesicular pathway to hepatic transport may be different among bile acids, and lithocholate-3-O-glucuronide seems to have higher accessibility to this transport system.

The effect of the co-infusion of ursodeoxycholate and its taurine conjugate, 3-O-glucuronide and 3,7-disulfate on estradiol-17 beta-glucuronide-induced cholestasis was examined. Estradiol-17 beta-glucuronide was intravenously administered to bile-drained rats at a rate of 0.075 mumol/min/100 g for 20 min. Co-infusion of ursodeoxycholate and its conjugates was simultaneously begun at a rate of 0.2 mumol/min/100 g and continued for 120 min. Ursodeoxycholate failed to improve and tauroursodeoxycholate only partially improved estradiol-17 beta-glucuronide-induced cholestasis between 20 and 40 min, although both bile acids increased bile flow after 80 min. Tauroursodeoxycholate increased biliary estradiol-17 beta-glucuronide excretion. Ursodeoxycholate-3-O-glucuronide completely inhibited cholestasis induced by estradiol-17 beta-glucuronide without changing biliary estradiol-17 beta-glucuronide excretion. Although ursodeoxycholate-3,7-disulfate had only a minor effect on cholestasis, it increased biliary excretion of estradiol-17 beta-glucuronide. In the Eizai hyperbilirubinuria rat (EHBR), a hyperbilirubinemic mutant Sprague-Dawley rat, the same dose of estradiol-17 beta-glucuronide failed to induce cholestasis with a marked delay in biliary excretion of estradiol-17 beta-glucuronide. In summary, ursodeoxycholate-3-O-glucuronide is more effective than tauroursodeoxycholate in inhibiting estradiol-17 beta-glucuronide-induced cholestasis and ursodoexycholate-3,7-disulfate had little effect. However, the unexpected effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate on excretion of estradiol-17 beta-glucuronide suggest that the interaction of these anions at the canalicular membrane is complicated, with interaction occurring at more than two pathways of the biliary excretion of these anions.

The effects of organic anions and bile acids on biliary lipid excretion were studied in EHBR, a hyperbilirubinemic mutant Sprague-Dawley rat. A marked delay in the biliary excretion of BSP, cefpiramide, rose bengal and ursodeoxycholate-disulfate was observed in these animals. The marked decrease in the biliary excretion of phospholipids and cholesterol and the uncoupling of biliary bile acids and lipids that occurred after the administration of BSP, cefpiramide and ursodeoxycholate-disulfate in control Sprague-Dawley rats was absent in EHBR. Rose bengal did not change biliary lipid excretion in either the control Sprague-Dawley rats or the EHBR. Although taurocholate markedly increased bile flow and biliary bile acid excretion in both types of rats, the increase in biliary lipid excretion observed in the control Sprague-Dawley rats was absent in EHBR. These findings indicate that EHBR have an impairment of hepatic lipid transfer that is enhanced by bile acids, possibly at the level of intracellular vesicular lipid transport.

We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hypothesis, UDC, UDC-3-O-glucuronide, UDC-3,7-disulfate and beta-muricholate were separately and intravenously infused into rats (1 mumol/min per 100 g), and biliary bicarbonate concentration was measured. The effects of these bile acids on biliary lipid secretion were also studied. All four bile acids increased bile flow and biliary bile acid excretion. UDC and beta-muricholate significantly increased biliary bicarbonate concentration, whereas UDC glucuronide and disulfate did not. Independence of UDC glucuronide excretion and biliary bicarbonate concentration was also confirmed in EHBR, a hyperbilirubinemic mutant Sprague-Dawley rat. In this case biliary bicarbonate concentration also increased in spite of the absence of UDC glucuronide in the bile after UDC infusion. Biliary phospholipid secretion was increased with UDC, unchanged with beta-muricholate, and decreased with UDC glucuronide and disulfate. Biliary cholesterol secretion was increased with UDC, unchanged with beta-muricholate and UDC glucuronide, and decreased with UDC disulfate. These data indicate that glucuronidation is not the cause of bicarbonate-rich hypercholeresis induced by UDC but that glucuronidation and sulfation change the effect of UDC on biliary lipid secretion.

A servo system including a microwave generator was applied to raise a rat's body temperature at a pre-set rate. Using this system the effects of age and the temperature elevation rate upon febrile seizures in rats were studied. The relationship between the brain GABA content and hyperthermia was also studied. From the results of the present study, the seizure occurrence rate was found to be highest at the age of 20 days, brain damage was speculated to be severe after hyperthermia-induced seizures with a slow temperature rise, and the regional GABA concentration in subcortical structures was found to increase during hyperthermia. These data indicate that a servo system with a microwave generator is useful for experimental febrile convulsions, and that GABA neurotransmission in subcortical structures might contribute to feed-back regulation against seizures during hyperthermia.

We report a case of multiple sclerosis in which CT showed multiple ring-like enhancement and butterfly-like distribution of a low density area with marginal enhancement. The latter finding is found in other demyelinating disorders but is less common in tumors or abscesses. Therefore, it seems to have some diagnostic value in multiple sclerosis.