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61.
Lamivudine, a nucleoside analogue, has been used widely as an effective antiviral agent for the treatment of patients with chronic hepatitis B virus (HBV) infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine occurs very frequently after long term therapy. We developed an oligonucleotide chip for the detection of YMDD motif mutants resistant to lamivudine and investigated the prevalence of the mutants in patients with chronic HBV infection who had not been treated by lamivudine before. Forty patients who had not been treated with lamivudine were included in this study. Serum samples were tested by the oligonucleotide chips designed for detection of wild-type YMDD motif, M552V and M552I. Samples were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. M552I mutants were detected by the oligonucleotide chips in 7.5% (3/40) of chronic HBV infected patients (2 chronic hepatitis and 1 cirrhosis). The results were in accordance with those of RFLP. YMDD motif mutants occur as natural genome variabilities in patients with chronic HBV infection who had not been treated with lamivudine before. Oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of mutants resistant to antiviral therapy in chronic HBV infection.  相似文献   
62.
This study is designed to investigate the effect of morphine on glutamate-induced toxicity of primary rat neonatal astrocytes. Glutamate decreases the intracellular GSH level, and thereby induces cytolysis of astrocytes and C6 glial cells accompanied by apoptotic features. Glutamate-induced cytotoxicity is protected by morphine and antioxidants such as GSH and NAC, whereas MK-801, an antagonist of glutamate receptor NMDA does not protect astrocytes against glutamate toxicity. Also, morphine antagonist, naloxone, as well as selective ligands for opioid receptor subtypes, including DAMGO, DPDPE, and U69593, do not inhibit the protective effect of morphine on glutamate-induced cytotoxicity. Morphine significantly prevents the depletion of GSH by glutamate and thereby inhibits the generation of H2O2 in a dose-dependent manner. Furthermore, morphine prevents the change of mitochondrial permeability transition by glutamate. Taken together, we suggest that morphine protects the primary rat neonatal astrocytes from glutamate toxicity via modulation of intracellular redox status.  相似文献   
63.
The peptides presented by major histocompatibility complex class I molecules adhere to strict rules concerning peptide length and occupancy by certain amino acid residues at anchor positions. Peptides presented by HLA-A*0201 molecules, for example, are generally nonapeptides requiring Leu or Met at position 2 and an aliphatic residue, predominantly Val, at position 9. A closely related molecule, HLA-A*0205, differing from the former at four amino acid residues, has a related but substantially different peptide motif. A*0205-presented peptides are still nonapeptides, and position 9 is still aliphatic, although it is preferentially occupied by Leu instead of Val. Position 2 not only allows aliphatic residues but also polar ones. Occupancy at position 6, considered as an auxiliary anchor in A*0201, as well as non-anchor residues at positions 3, 4, and 8 are relatively well conserved between the two peptide motifs. Thus, although a number of the T cell epitopes presented by the two HLA-A2 forms is expected to be identical, a considerable number of epitopes should be different.  相似文献   
64.
PurposeOral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD.Materials and MethodsA seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels.ResultsSignificantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120.ConclusionDW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).  相似文献   
65.
Although there have been some reports that measured the size of mastoid pneumatization, only a few studies have reported the age-related variations in the mastoid air cell system using three-dimensional (3D) reconstruction techniques of computed tomography (CT) images. We performed a retrospective, cross-sectional study. A 3D reconstruction based on CT images was performed on 199 ears of 102 patients (age range 6–84 years) without otologic disease by a surface-rendering algorithm. The results showed that mastoid pneumatization continued to grow until the third decade. Thereafter, it declined slowly, and then rapidly after the seventh decade. No statistically significant difference was found between male and female or between right and left sides. There was a significant difference between the larger and smaller sides of individuals. The volume measurement technique based on the 3D reconstruction technique reported here is widely available, highly accurate and easy to perform.  相似文献   
66.
The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.  相似文献   
67.
Increased expression of glucose transporter1 (GLUT1) has been reported in many human cancers. We hypothesized that the degree of GLUT1 might provide a useful biological information in gastric adenocarcinoma. RT-PCR and immunostaining were used to analyze GLUT1 expression in gastric cancer. RT-PCR showed GLUT1 expression was not largely detected in normal gastric tissue but was detected in cancerous gastric tissue of counterpart. By immunohistochemistry, GLUT1 protein was absent in normal gastric epithelium and intestinal metaplasia. 11 of 65 patients with gastric adenocarcinoma had specific GLUT1 immunostaining in a plasma membrane pattern with varied intensities. GLUT1 protein did not show any significant correlation with tumor stage and nodal metastasis (p>0.05 by Mann-Whitney test). However, the positive immunostaining for GLUT1 is associated with intestinal differentiation (p=0.003). Our results suggest that GLUT1 protein is associated with intestinal type of gastric cancer.  相似文献   
68.
Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3- p22 in the late event may be involved in the laryngeal carcinogenesis.  相似文献   
69.
One of the major limitations in the current set of techniques available to neuroscientists is a dearth of methods for imaging individual cells deep within the brains of live animals. To overcome this limitation, we developed two forms of minimally invasive fluorescence microendoscopy and tested their abilities to image cells in vivo. Both one- and two-photon fluorescence microendoscopy are based on compound gradient refractive index (GRIN) lenses that are 350-1,000 microm in diameter and provide micron-scale resolution. One-photon microendoscopy allows full-frame images to be viewed by eye or with a camera, and is well suited to fast frame-rate imaging. Two-photon microendoscopy is a laser-scanning modality that provides optical sectioning deep within tissue. Using in vivo microendoscopy we acquired video-rate movies of thalamic and CA1 hippocampal red blood cell dynamics and still-frame images of CA1 neurons and dendrites in anesthetized rats and mice. Microendoscopy will help meet the growing demand for in vivo cellular imaging created by the rapid emergence of new synthetic and genetically encoded fluorophores that can be used to label specific brain areas or cell classes.  相似文献   
70.
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