赖氨酰氧化酶与人类疾病

赖氨酰氧化酶(lysyl oxidases,LOXs)是一种能够催化细胞外基质蛋白(如胶原和弹性蛋白)交叉连接的酶类,这一功能使其在组织的稳定、重塑和伤口愈合中发挥重要作用.随着研究的不断深入,LOXs在细胞增殖、细胞趋化以及肿瘤发生等过程中也彰显出十分关键的作用.研究发现,一些诸如结缔组织病、剥脱综合症、铜代谢障碍性疾病及盆腔器官脱垂和骨疾等疾病的发生与LOXs有很大关系.综述了LOXs的生物合成、结构特点、多功能性以及与人类疾病的关系.     

Identification of cellular isoform of oviduct-specific glycoprotein: role in oviduct tissue remodeling?

The oviduct is known to secrete mucins (MUC1 and MUC9) under the influence of ovarian steroids. The secreted form of MUC1 binds gametes in the oviduct, whereas the cellular form seen in breast cancers has been implicated in cell adhesion and morphogenesis. The secreted MUC9 or oviduct-specific glycoprotein (OGP), in addition to being a mucin, belongs to family 18 glycosylhydrolases and is known to bind gametes and embryos in the oviduct. Studies in our laboratory have identified non-muscle myosin IIA (involved in cell shape, polarity, and morphogenesis) as the protein partner to OGP in gametes. In view of the crucial role of the cortical cytoskeleton in the selective internalization of tight junctions (TJs) /adherent junctions (AJs) or apical junctional complex (AJC) in simple epithelial cells during tissue remodeling, the present study has been undertaken to evaluate the existence of a cellular form of OGP in oviductal tissue, which itself undergoes cyclic tissue remodeling. In silico analysis of the deduced amino-acid sequence of OGP has revealed the presence of several conserved motifs; these imply that OGP is a component of multi-protein complexes such as TJs. Corroborative immunoelectron-microscopic analysis in peri-ovulatory oviduct epithelia in the bonnet monkey has revealed the presence of OGP at the TJ. Co-localization studies of OGP and cadherin demonstrate that, whereas OGP is localized at the tonofilaments of the TJs, cadherin is localized at the intercellular space of the AJ. The possible role of OGP in oviductal tissue remodeling is discussed in light of the present findings and those reported in the literature. This study was supported by funds from the Indian Council for Medical Research and by senior research fellowships (to K. Kadam) from the Council for Scientific and Industrial Research.     

Emergence of an unrelated highly aberrant clone in an AML patient at relapse four months after peripheral blood stem cell transplantation

We report a case of AML-M1 with 5q aberration at diagnosis. The patient was treated with high-dose chemotherapy (HDCT). After remission induction, he received allogenic peripheral blood stem cell transplantation (PBSCT) from an HLA-match donor brother. The successive follow-up conventional cytogenetics investigations in remission after HDCT and PBSCT revealed cytogenetic remission. The most interesting observation in this case is that relapsed marrow revealed the emergence of an entirely new, highly aberrant, unrelated clone with unusual translocations t(6;17)(p23;p11.2),+8,der(8)dup inv(8)(q23qter), t(10;19)(q26;q13.3) 4½ months after PBSCT. Our findings suggest the possibility of a mutagenic effect of HDCT and myeloablative intense chemotherapy before PBSCT that could have induced a genetic lesion in the recipient''s genetically unstable stem cells in an environment of immunosuppression. The highly complex nature of the clone and the rapid clonal evolution indicates the possibility of selective pressure with proliferative advantage.     

Radiation dose measurements in a dental orthopantogram unit using indigenously developed optically stimulated luminescence dosimeters

Dental orthopantogram (OPG)/cone beam computed tomography (CBCT) scanners are gaining popularity due to their 3D imaging with multiplanar view that provides clinical benefits over conventional dental radiography systems. Dental OPG/CBCT provides optimal visualization of adjacent overlaying anatomical structures that will be superpositioned in any single projection. The characteristics of indigenously developed optically stimulated luminescence dosimeters, namely, aluminium oxide doped with carbon (Al₂O₃:C), lithium magnesium phosphate doped with terbium and boron (LiMgPO₄:Tb,B) and lithium calcium aluminium fluoride doped with europium and yttrium (LiCaAlF₆:Eu,Y) were evaluated for their use in dental dosimetry. The dose?response of these dosimeters was studied at X‐ray energies 60 kV, 70 kV and 81 kV. Radiation doses were also measured using Gafchromic film for comparison. Radiation dose was measured at eight different locations of a polymethyl methacrylate (PMMA) head phantom including eyes. The optically stimulated luminescence (OSL) sensitivity of LiMgPO₄:Tb,B is about 1.5 times and LiCaAlF₆:Eu, is about 20 times higher than the sensitivity of Al₂O₃:C. It was found that measured radiation doses by the three optically stimulated luminescence dosimeters (OSLDs) and Gafchromic film in the occipital region (back side) of a PMMA phantom, were consistent but variations in dose at other locations were significantly higher. The three OSLDs used in this study were found to be suitable for radiation dose measurement in dental units.     

Synthesis and luminescence study of Eu3+‐doped SrYAl3O7 phosphor

Rare‐earth ions play an important role in eco‐friendly solid‐state lighting for the lighting industry. In the present study we were interested in Eu³⁺ ion‐doped inorganic phosphors for near ultraviolet (UV) excited light‐emitting diode (LED) applications. Eu³⁺ ion‐activated SrYAl₃O₇ phosphors were prepared using a solution combustion route at 550°C. Photoluminescence characterization of SrYAl₃O₇:Eu³⁺ phosphors showed a 612 nm emission peak in the red region of the spectrum due to the ⁵D₀→⁷F₂ transition of Eu³⁺ ions under excitation at 395 nm in the near‐UV region and at the 466 nm blue excitation wavelength. These red and blue emissions are supported for white light generation for LED lighting. Structure, bonding between each element of the sample and morphology of the sample were analysed using X‐ray diffraction (XRD) and scanning electron microscopy (SEM), which showed that the samples were crystallized in a well known structure. The phosphor was irradiated with a ⁶⁰Co‐γ (gamma) source at a dose rate of 7.2 kGy/h. Thermoluminescence (TL) studies of these Eu³⁺‐doped SrYAl₃O₇ phosphors were performed using a Nucleonix TL 1009I TL reader. Trapping parameters of this phosphor such as activation energy (E), order of kinetics (b) and frequency factor (s) were calculated using Chen's peak shape method, the initial rise method and Ilich's method.     

Luminescence study of LiMgBO3:Dy for γ‐ray and carbon ion beam exposure

LiMgBO₃:Dy³⁺, a low Z_eff material was prepared using the solution combustion method and its luminescence properties were studied using X‐ray diffraction (XRD), scanning electron microscopy (SEM), thermoluminescence (TL), photoluminescence (PL), Fourier transform infrared spectroscopy, and electron paramagnetic resonance (EPR) techniques. Reitvield refinement was also performed for the structural studies. The PL emission spectra for LiMgBO₃:Dy³⁺ consisted of two peaks at 478 due to the ⁴F_9/2→⁶H_15/2 magnetic dipole transition and at 572 nm due to the hypersensitive ⁴F_9/2→⁶H_13/2 electric dipole transition of Dy³⁺, respectively. A TL study was carried out for both the γ‐ray‐irradiated sample and the C⁵⁺ irradiated samples and was found to show high sensitivity for both. Moreover the γ‐ray‐irradiated LiMgBO₃:Dy³⁺ sample showed linearity in the dose range 10 Gy to 1 kGy and C⁵⁺‐irradiated samples show linearity in the fluence range 2 × 10¹⁰ to 1 × 10¹¹ ions/cm². In the present study, the initial rise method, various heating rate method, the whole glow curve method, glow curve convolution deconvolution function, and Chen's peak shape method were used to calculate kinetic parameters to understand the TL glow curve mechanism in detail. Finally, an EPR study was performed to examine the radicals responsible for the TL process.     

Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

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