Lattice Parameter of Titanium Monoxides under High Pressure

The effect of pressure on the crystal structure and the lattice parameter of vacancy rich titanium monoxides has been studied using a high pressure apparatus of the tetrahedral anvil type combined with an X-ray diffraction equipment. Two kinds of specimens, TiO_ and TiO_, have been used, the former containing most of vacancies in the oxygen sublattice and the latter in the titanium sublattice. Up to the pressure of 60 kbar, no significant change in the crystal structure has been observed. The change in the lattice parameter with increasing pressure is unexpectedly small for both the specimens, but a minor difference between them has been observed. An initial change is larger in TiO_ than in TiO_, while in the pressure range between 10 and 60 kbar the latter shows faster decrease. The experimental results are discussed in relation to the behavior of the vacancies under high pressure

Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney

Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney.BackgroundIndoxyl sulfate is a uremic toxin that accumulates in the body because of the patient's inability to excrete it and it induces a number of uremic symptoms and leads to chronic renal failure. The functional failure of the excretion system for indoxyl sulfate causes its accumulation in blood. The purpose of the present study was to characterize the transport mechanism responsible for the renal excretion of indoxyl sulfate.MethodsThe [3H]indoxyl sulfate transport mechanism was investigated using an in vivo tissue-sampling single-injection technique, the kidney uptake index (KUI) method. Rat organic anion transporter 3 (rOAT3)-expressing Xenopus laevis oocyte system was used for measuring [3H]indoxyl sulfate uptake activity.ResultsProbenecid showed a concentration-dependent inhibitory effect on the uptake of [3H]indoxyl sulfate using the KUI method, and uptake was inhibited by organic anions such as para-aminohippuric acid (PAH) and benzylpenicillin, by weak base such as cimetidine, and by uremic toxins, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and hippuric acid (HA). However, salicylic acid, indomethacin, 3,5,3′-triiodo-L-thyronine and indole acetic acid (IA) had no effect on the uptake. rOAT3-expressing oocytes exhibited uptake of [3H]indoxyl sulfate by rOAT3 (Km = 158 μmol/L). Moreover, a number of uremic toxins inhibited the uptake of [3H]indoxyl sulfate by rOAT3.ConclusionsThese results suggest that rOAT3 is responsible for the renal uptake of indoxyl sulfate, and uremic toxins share the transport mechanism for indoxyl sulfate. Mutual inhibition of these uremic toxins via OAT3 may accelerate their accumulation in the body and, thereby, the progression of nephrotoxicity in uremia

Kinetic evidence for active efflux transport across the blood-brain barrier of quinolone antibiotics.

ABSTRACT A distributed model has been used to clarify the mechanism of the restricted and differential distribution of the quinolone antibiotics in the rat central nervous system (CNS). The symmetrical permeability clearances across the blood-brain barrier (BBB), PS BBB , and across the blood-cerebrospinal fluid barrier (BCSFB), PS CSF , and the active efflux clearances across the BBB, PS BBB,eff , were obtained from a nonlinear least squares regression analysis combined with the fast inverse Laplace transforming program for in vivo data. The values of PS BBB,eff were 10-to 260-fold greater than those of PS BBB , providing kinetic evidence to support the hypothesis that a significant efflux transport across the BBB is responsible for the limited distribution of quinolones in brain tissue. Moreover, by simulation studies, we could demonstrate the concentration profiles in the brain as a function of the distance from the ependymal surface. However, active efflux transport across the BCSFB has been suggested to have only a slight effect on the apparent elimination from the cerebrospinal fluid. Comparing the apparent brain tissue-to-unbound serum concentration ratio at steady state, it has been suggested that the net flux across the BBB, i.e., the ratio of PS BBB to the sum of PS BBB and PS BBB,eff , is a determinant for the differential distribution of these quinolones in brain tissue. Such a putative active efflux transport system would play a significant role in decreasing the brain interstitial fluid concentration of quinolones. The side effect of quinolone antimicrobial agents (quinolones) on the CNS such as confusion, hallucinations, anxiety, agitation, depression and convulsive seizures is one of the most serious problems associated with their use as chemotherapeutic agents The present study investigated the process governing the restricted distribution of quinolones in the CNS based on the distributed model. In this study, we determined the initia

Contribution of the LIM Domain and Nebulin-Repeats to the Interaction of Lasp-2 with Actin Filaments and Focal Adhesions

Lasp-2 binds to actin filaments and concentrates in the actin bundles of filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s) responsible for its interactions with actin filaments and focal adhesions are still unclear. In this study, we revealed that the N-terminal fragment from the LIM domain to the first nebulin-repeat module (LIM-n1) retained actin-binding activity and showed a similar subcellular localization to full-length lasp-2 in neural cells. The LIM domain fragment did not interact with actin filaments or localize to actin filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to filopodial actin bundles. Although truncation of the LIM domain caused the loss of F-actin binding activity and the accumulation of filopodial actin bundles, these truncated fragments localized to focal adhesions. These results suggest that lasp-2 interactions with actin filaments are mediated through the cooperation of the LIM domain and the first nebulin-repeat module in vitro and in vivo. Actin filament binding activity may be a major contributor to the subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2 recruitment to focal adhesions

Deformation around neutron-rich Cr isotopes in axially symmetric Skyrme-Hatree-Fock-Bogoliubov method

We analyse deformation mechanism in neutron-rich Cr, Fe and Ti isotopes with N=32-44 by means of a Skyrme-Hartree-Fock-Bogoliubov mean-field code employing a two-dimensional mesh representation in the cylindrical coordinate system. Evaluating systematically the quadrupole deformation energy, we show that the Skyrme parameter set SkM* gives a quadrupole instability around the neutron number N$\sim$38-42 in Cr isotopes, where the deformation energy curve suggests a transitional behavior with a shallow minimum extending to a large prolate deformation. Roles of a deformed N=38 gap and the position of the neutron g9/2 orbit are analysed in detail

Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

Background: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response wit

A Case Report of Matrix-Producing Carcinoma of the Breast during Lactation : A secondary publication

Matrix-producing carcinoma (MPC) of the breast is relatively rare. We report on a case of MPC of the breast during lactation. A female in her 30s noticed a lump in the upper inner and outer quadrants of her left breast 9 months into her pregnancy. She came hospital at one month after delivery. Ultrasonography revealed a hypoechoic tumor with an unclear border region. An MRI revealed a breast tumor approximately 19 mm in size, with dynamic studies demonstrating early contrast and ring enhancement. A core needle biopsy was performed, resulting in an histopathological diagnosis of invasive carcinoma ［Estrogen receptor-, Progesterone receptor-, Human epidermal growth factor receptor 2(HER2)-; stage I, T1cN0M0］. Breast-conserving surgery and a sentinel lymph node biopsy (SLNB) were performed. The SLNB was negative for cancer. Chemotherapy (FEC100, DTX75) and radiotherapy were performed as adjuvant therapies. Seventeen months after surgery, the patient is recurrence-free