Some problems on Palaeozoic-Mesozoic tectonics inSouthwest Japan: Tectonics of metamorphic belts of high-pressure type

Tectonics of the Sangun belt and Sambagawa belt in Southwest Japan, which belong to the metamorphic belt of high-pressure type, have been discussed in this paper. Regarding the Sangun belt, the tectonics of the phases when the original rocks of the Sangun belt were deposited and the Sangun metamorphic field appeared have been analysed. As for the Sambagawa belt, the tectonics of the phases when the Sambagawa metamorphic field was placed under the condition of the highest temperature and then its collapse began have been analysed

Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance

Endometrial carcinoma often arises from normal endometrial glandular cells via a precursor, atypical endometrial hyperplasia. However, the genetic changes involved in this carcinogenetic process are not fully understood. Differentially expressed genes were selected from glandular cells of normal proliferative-phase endometria, atypical endometrial hyperplasia, and endometrial carcinoma using laser-captured microdissection and microarray. The microarray analysis revealed a total of 51 genes to be up-regulated and 23 genes to be down-regulated in neoplastic endometrial epithelia. We focused on lipocalin2 (LCN2), which showed the largest magnitude of up-regulation. Immunostaining for lipocalin2 confirmed a stepwise increase in its expression in endometrial hyperplasia and carcinoma. In addition, elevated expression of lipocalin2 was correlated with the poor outcome of endometrial carcinoma patients. The subcellular distribution of lipocalin2 was both cytoplasmic and nuclear, despite reports that lipocalin2 is a secretory protein. Treatment of endometrial carcinoma cells with 5-azacytidine increased the expression of lipocalin2, suggesting the expression to be controlled by methylation of the promoter. The forced expression of lipocalin2 resulted in the enhanced cell proliferation and invasion in vitro. The expression of lipocalin2 increased with the endometrial carcinogenesis, and accumulation of the protein conferred biological aggressiveness to endometrial carcinoma cells. These results suggest lipocalin2 to be a novel target in the treatment of endometrial carcinoma.ArticleHUMAN PATHOLOGY. 42(9):1265-1274 (2011)journal articl

Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma

Copyright (c) 2010 Taylor & Francis. This is an electronic version of an article published in "GYNECOLOGICAL ENDOCRINOLOGY, Volume 26, Issue 3, pages 220-229 (2010)". GYNECOLOGICAL ENDOCRINOLOGY is available online at: https://doi.org/10.3109/09513590903215482Cyclin-dependent-kinase (cdk) inhibitor, p27<SUKip1</SU (p27), has been shown to participate in progestin-induced growth suppression of normal endometrial glands. To analyse the molecular mechanisms regulating p27 protein, we examined immunohistochemical expression of the SCF<SUSkp2</SU (Skp1-Cullin-F-box protein) complex factors, i.e. Skp1, Cul1 and Skp2, and compared them with that of p27, steroid receptors and Ki-67. In normal endometrial glands, the expression of Skp2 was observed in the proliferative phase, whereas that of p27 was observed in the secretory phase. Cultured normal endometrial glandular cells showed that progesterone induced the down-regulation of Skp2 along with up-regulation of p27. In endometrial carcinomas, the inverse topological correlation between Skp2 and p27 was evident in 39/66 (59%) cases, and the expression of Skp2 showed a strong correlation with Ki-67. These findings suggest that the expression of SCF<SUSkp2</SU complex changes during the menstrual cycle in normal endometrium and the SCF<SUSkp2</SU ubiquitin-proteasome pathway may also work in endometrial carcinomas.</.ArticleGYNECOLOGICAL ENDOCRINOLOGY. 26(3):220-229 (2010)journal articl

Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy mainly caused by heterozygous mutations in the SCN1A gene encoding a voltage-gated sodium channel Nav1.1. We previously reported dense localization of Nav1.1 in parvalbumin (PV)-positive inhibitory interneurons in mice and abnormal firing of those neurons in Nav1.1-deficient mice. In the present study, we investigated the physiologic consequence of selective Nav1.1 deletion in mouse global inhibitory neurons, forebrain excitatory neurons or PV cells, using vesicular GABA transporter (VGAT)-Cre, empty spiracles homolog 1 (Emx1)-Cre or PV-Cre recombinase drivers. We show that selective Nav1.1 deletion using VGAT-Cre causes epileptic seizures and premature death that are unexpectedly more severe than those observed in constitutive Nav1.1-deficient mice. Nav1.1 deletion using Emx1-Cre does not cause any noticeable abnormalities in mice; however, the severe lethality observed with VGAT-Cre-driven Nav1.1 deletion is rescued by additional Nav1.1 deletion using Emx1-Cre. In addition to predominant expression in PV interneurons, we detected Nav1.1 in subpopulations of excitatory neurons, including entorhino-hippocampal projection neurons, a subpopulation of neocortical layer V excitatory neurons, and thalamo-cortical projection neurons. We further show that even minimal selective Nav1.1 deletion, using PV-Cre, is sufficient to cause spontaneous epileptic seizures and ataxia in mice. Overall, our results indicate that functional impairment of PV inhibitory neurons with Nav1.1 haploinsufficiency contributes to the epileptic pathology of Dravet syndrome, and show for the first time that Nav1.1 haploinsufficiency in excitatory neurons has an ameliorating effect on the pathology

Tectonic Evolution of the Sambagawa Schists and its Implications in Convergent Margin Processes

The Sambagawa schists as high P /T metamorphic rocks are a member of Mesozoic accretionary complexes developed in the southern front of the Kurosegawa-Koryoke continent of Southwest Japan. The Mesozoic accretionary complexes are divided into four megaunits developed as nappes, Chichibu megaunit II, Sambagawa megaunit, Chichibu megaunit I and Shimanto megaunit in descending order of structural level. The Chichibu megaunit II consists of three accretionary units developed as nappes, late early Jurassic unit, late middle Jurassic unit and latest Jurassic unit (Mikabu unit) in descending order of structural level. The Chichibu megaunit I consists of five accretionary units developed as nappes, late middle Jurassic unit (Niyodo unit), late Jurassic unit, Valanginian unit, Barremian unit and Albian unit in descending order of structural level. The Shimanto megaunit, which just underlies the Chichibu megaunit I, is Cenomanian-Turonian accretionary unit and Coniacian-Campanian accretionary unit. The schists, which underlie the Chichibu megaunit II, all have been so far called the Sambagawa schists. These are divided into six units, Saruta unit, Fuyunose unit, Sogauchi unit, Sakamoto unit, Oboke unit and Tatsuyama unit in descending order of structural level, which show different tectono-metamorphic history and different radiometric ages from each other. The Sakamoto unit, Oboke unit and Tatsuyama unit have been assumed with reference to their radiometric ages and structural relations to belong to the late middle Jurassic accretionary unit of the Chichibu megaunit I (high pressure equivalent of the Niyodo unit), the Cenomanian-Turonian accretionary unit of the Shimanto megaunit and the Coniacian-Campanian accretionary unit of the Shimanto megaunit respectively in this paper. The upper member of the Sambagawa schists, Saruta unit, Fuyunose unit and Sogauchi unit, is therefore called the Sambagawa megaunit in this paper. The northern half and the southern half of the Sambagawa megaunit are intercalated as nappes between the Chichibu megaunit II and the Oboke unit and between the Chichibu megaunit II and the Sakamoto unit respectively. The constituent units of the Chichibu megaunit II, Sambagawa megaunit and Shimanto megaunit clearly show a downward younging age polarity, as compared with each other with reference to the oldest one of radiometric ages ( = metamorphic ages) of each unit. The Chichibu megaunit II and the Chichibu megaunit I show the same radiometric ages as compared between them with the same fossil age. The Saruta unit, Fuyunose unit and Sogauchi unit have therefore been assumed to be high pressure equivalent of Valanginian unit, that of Barremian unit and that of Albian unit of the Chichibu megaunit I respectively. These high pressure units were exhumed, separating the Chichibu supermegaunit into the Chichibu megaunit II and the Chichibu megaunit I and thrusting up onto the Chichibu megaunit I. On the basis of the growth history of amphibole in hematite-bearing basic schists of the Sambagawa megaunit, it has been assumed that the highest temperature metamorphism of the Fuyunose unit occurred, when it had been coupled with the Saruta unit which was exhuming, and that of the Sogauchi unit did through its coupling with the Fuyunose and Saruta units which were exhuming. In the subduction zone which was responsible for the formation of the Sambagawa megaunit, namely, the peak metamorphism of a newly subducted unit appears to have occurred when it had been coupled with previously subcreted units which were exhuming. It has been also clarified that the subduction of a new unit occurred mixing the lower pressure part of the pre-existing subcretion unit as tectonic blocks. There is a distinct difference in the oldest one of radiometric ages between constituent units of the Sambagawa schists, showing a downward younging age polarity. The oldest one of radiometric ages of each unit appears to approximate to the age of the ending of peak metamorphism and to the age (Eh age) of the beginning of its exhumation. Such the tectonics of the Sambagawa megaunit would be explained in term of two-way street model. Because the age (Sub age) of the beginning of the subduction of each unit can be assumed from its fossil age, the average velocity of the subduction and that of the exhumation of the Sambagawa megaunit in Shikoku have roughly been estimated to be ca. 0.9 mm/year and ca. 2.0 mm/year respectively. Deformation of quartz, whose style depends strongly upon strain rate, resulted in type I crossed girdle without conentration in Y even in the depth part of more than 10kb of the subduction zone, which was placed under temperature condition of much higher than 500°C, unlike the cases of magma-arcs where quartz c-axis fabrics with maximum concentration in Y are found in gneisses produced under temperature condition of lower than 500°C. Quartz deformation in the depth part of 15-17kb of the subduction zone appears to have occurred as dominant prism slip. The hanging wall of the Kurosegawa-Koryoke continent, which was placed at the depth of ca. 15-17 kb, thrust onto the Saruta unit at the depth of ca. 10-11 kb, accompanying intermingling of constituent rocks of the former and the latter and also mixing of various depth parts of the latter. The highest temperature metamorphism of the Saruta unit, which appears to have occurred under metamorphic condition of lower P /T than under that related to the formation of the general type of high P /T type metamorphic rocks, is ascribed to a contact metamorphism related to the overthrusting of the Kurosegawa-Koryoke continent. The thrusting of the Kurosegawa-Koryoke continent is ascribed to its collision with the Hida continent. The coupling of the previously subcreted Saruta unit with the newly subcreted Fuyunose unit occurred accompanying nearly isobaric cooling of the former. The great exhumation of the Saruta nappe (I + II) and Fuyunose nappe schists with great volume began together with the subcretion of the Sogauchi unit. The beginning age of the exhumation of the Sambagawa schists with great volume appears to coincide with that of the subduction of the Kula-Pacific ridge in Kyushu-Shikoku, which has been assumed by Kiminami et al. (1990). Namely, their great exhumation occurred with the progress of the subduction of the Kula-Pacific ridge with an eastward younging age polarity. The exhumation units, which were developed after the Mikabu unit, clearly show an eastward younging age polarity. Namely, these comparable with the Saruta unit, Fuyunose unit and Sogauchi unit are not found in central Japan and the Kanto Mountains. Rock deformation in the deformation related to the exhumation of the Sambagawa schists and their underlying schists appears to have commonly been of flattened type in mean strain. During the Ozu phase when the Kula-Pacific ridge subducted to the greater depth, the collapse of the Kurosegawa-Koryoke continent took again place, accompanying that of the pile nappe structures of the Sambagawa megaunit, Chichibu megaunit I and Oboke unit, and the thermal gradient along the plate boundary greatly changed, giving rise to medium P/T type metamorphism in the subduction zone (formation of the Tatsuyama nappe schists). The geological structures of the Sambagawa megaunit consist thus of two types of pile nappe structures, pre-Ozu phase pile nappe structures and Ozu phase pile nappe structures. The former is structures related to the coupling of the exhuming units ( = previously subcreted units) with the newly subcreted unit. The latter is structures showing the collapse of the former. The Ozu phase pile nappe structures are further divided into the pile nappe structures formed during the earlier stage (Tsuji stage) of the Ozu phase and these formed during the later stage (Futami stage). The former is disharmonic with reference to movement picture with the latter: The deformation related to the formation of the former, accompanying exhumation of the Oboke nappes, appears to contain a component of northward displacement, while that for the latter does a component of southward displacement. After the Ozu phase deformation the Sambagawa megaunit suffered the Hijikawa-Oboke phase folding, forming a series of sinistral en echelon upright folds. The relationship between the above-mentioned tectonic events of the Sambagawa megaunit and its surroundings and their radiometric ages is summarized as follows: [Original table is skipped. For more details, please refer to the full text.

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ -

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. Patients and Methods: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. Results: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. Conclusions: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary