Molecular Pathology of Murine Ureteritis Causing Obstructive Uropathy with Hydronephrosis

Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents

Cardiovascular and respiratory effects of the degree of head-down angle during robot-assisted laparoscopic radical prostatectomy

Background: Robot-assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis. Methods: Forty-seven ASA physical status 1 and 2 patients underwent open retropubic radical prostatectomy (RRP) or RALP. Patients receiving RALP were randomized to undergo the operation in the 20°, 25° or 30° Trendelenburg position. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end-tidal CO2 pressure (PetCO2), tidal volume (Vt), peak inspiratory pressure (PIP) and dynamic compliance (Cdyn) were recorded during the operation. Results: Angle of head-down tilt was significantly correlated with MAP, PIP and Cdyn, but not with HR, RR or PetCO2. MAP decreased gradually over time in each group in the Trendelenburg position with pneumoperitoneum. As the angle of head-down tilt became stronger, MAP, RR, PetCO2 and PIP tended to increase and Cdyn tended to decrease. Conclusions: This study demonstrated that the degree of the head-down angle at RALP affected the cardiovascular and respiratory parameters. Pneumoperitoneum with head-down position in RALP influenced the cardiovascular and respiratory system to a greater extent than RRP, and these effects were stronger with deeper head-down angle. © 2013 John Wiley & Sons, Ltd

Hydrogeological responses to incoming materials at the erosional subduction margin, offshore Osa Peninsula, Costa Rica

Bulk mineral assemblages of sediments and igneous basement rocks on the incoming Cocos Plate at the Costa Rica subduction zone are examined by X-ray diffraction analyses on core samples. These samples are from Integrated Ocean Drilling Program Expedition 334 reference Site U1381, ∼ 5 km seaward of the trench. Drilling recovered approximately 100 m of sediment and 70 m of igneous oceanic basement. The sediment includes two lithologic units: hemipelagic clayey mud and siliceous to calcareous pelagic ooze. The hemipelagic unit is composed of clay minerals (∼50 wt.%), quartz (∼5 wt.%), plagioclase (∼5 wt.%), calcite (∼15 wt.%) and ∼30 wt.% of amorphous materials, while the pelagic unit is mostly made up of biogenic amorphous silica (∼50 wt.%) and calcite (∼50 wt.%). The igneous basement rock consists of plagioclase (∼50–60 wt.%), clinopyroxene (∼>25 wt.%), and saponite (∼15–40 wt.%). Saponite is more abundant in pillow basalt than in the massive section, reflecting the variable intensity of alteration. We estimate the total water influx of the sedimentary package is 6.9 m³/yr per m of trench length. Fluid expulsion models indicate that sediment compaction during shallow subduction causes the release of pore water while peak mineral dehydration occurs at temperatures of approximately ∼100°C, 40–30 km landward of the trench. This region is landward of the observed updip extent of seismicity. We posit that in this region the presence of subducting bathymetric relief capped by velocity weakening nannofossil chalk is more important in influencing the updip extent of seismicity than the thermal regime.This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons, Inc. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/journal/10.1002/%28ISSN%291525-2027/Keywords: Costa Rica margin, diagenesis, CRISP, seismicityKeywords: Costa Rica margin, diagenesis, CRISP, seismicit

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining (NHEJ) repair. Impaired NHEJ is well known to cause genomic instability, including development of T-cell malignancies in KU70- and KU80-deficient mice. Collectively, our work has uncovered important roles for TOX in regulating NHEJ by elevating genomic instability during leukemia initiation and sustaining leukemic cell proliferation following transformation

Quantitative and Qualitative Urinary Cellular Patterns Correlate with Progression of Murine Glomerulonephritis

The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology

沈み込み帯に持ち込まれる物質に含まれる生物起源非晶質シリカがプレート境界断層の摩擦特性に与える影響

京都大学0048新制・課程博士博士(理学)甲第20925号理博第4377号新制||理||1628(附属図書館)京都大学大学院理学研究科地球惑星科学専攻(主査)教授 田上 高広, 教授 下林 典正, 准教授 河上 哲生学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

Expression and distribution of inducible nitric oxide synthase in mouse testis

Nitric oxide (NO) is a simple and relatively unstable radical under physiological conditions. It is synthesized by three isoforms of NO synthase, that is neuronal, endothelial and inducible (iNOS) isoforms. In the present study, we investigated the distribution of iNOS with immunohistochemical methods in the mouse testis. The iNOS-immunoreactivity was detected on the basal region of the seminiferous tubules, where the cytoplasm of Sertoli cells was selectively immunolabeled. This immunoreactivity was observed by both immunofluorescent and immunoenzyme methods. Weak immunoreactivity was detected on the perinuclear cytoplasm of Sertoli cells throughout the seminiferous stages, whereas in stages I-VIII, it was remarkable on the processes of Sertoli cells surrounding the spermatogonia and early spermatocytes, and elongating into the lumina of seminiferous tubules. By reverse transcriptase-polymerase chain reaction, mRNA for iNOS was found to be expressed in the mouse testis. These results reveal that iNOS is consistently distributed at the front of the testicular environment

Exon skipping of exonuclease 1 in MRL/MpJ mice is caused by a nucleotide substitution of the branchpoint sequence in intron eight

In MRL/MpJ mice, there is a genetic mutation of exonuclease 1 (Exo1), in which the exon 9 is sometimes deleted. In the presentstudy, to check the generation ofthe spliced exons, exon 8-intron 8-exon 9 (pCX/Ex/EIE/B and pCX/Ex/EIE/M) plasmids were temporally transfected in vitro into BALB 3T3 cells, and RT-PCR using appropriate primer pair was carried out 1 day after transfection. In these constructions, pCX/Ex/EIE/B was derived from genomic sequence of C57BL/6 mice, and pCX/Ex/EIE/M was from MRL/MpJ. A spliced band was detected in pCX/Ex/EIE/B, but was present little or very weakly in pCX/Ex/EIE/M. Next, the same spliced band was demonstrated in the pCX/Ex/EIE/M(T) plasmid, in which the branchpoint sequence (BPS) of pCX/Ex/EIE/M including the exon 9 was changed into that of pCX/Ex/EIE/B. The splicing did not occur in the del1/B mutant, in which 1960 nucleotides of the intron 8 were deleted, whereas it was detected in the del2/B plasmid deleted 1036 nucleotides in its middle region. These results suggest that the nucleotide T to A mutation of the BPS in the intron 8 is at least a sufficient for generation of splice variants (tr-1 and tr-2 Exo1)

Genomic analysis of the appearance of testicular oocytes in MRL/MpJ mice

Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y^[MRL]), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study, we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and 2 consomic strains, male B6-Y^[MRL] and MRL-Y^[B6]. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y^[B6] mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least 1 other causative gene on the MRL-type autosomes (MRL testicular oocyte production; mtop) other than that on Y^[MRL]. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8-17cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y^[MRL]