Alteration of E-cadherin and beta-catenin in mouse vestibular epithelia during induction of apoptosis

The aim of this study was to examine if adhesion molecules had relation with degeneration and regeneration processes of mammalian vestibular epithelia. The distribution of E-cadherin and beta-catenin was immunohistochemically examined in normal and aminoglycoside-treated utricles of mice. E-cadherin and beta-catenin linearly expressed between epithelial cells in normal specimens. Aminoglycoside injury resulted in temporal alteration in distribution of these molecules with induction of apoptosis in hair cells. Degradation of both molecules was widely observed in vestibular epithelia, while some supporting cells exhibited accumulation of beta-catenin. After completion of induction of apoptosis, expression of these adhesion molecules was normal in distribution. These findings suggest that the E-cadherin-beta-catenin complex plays roles in degeneration and subsequent repair processes in vestibular epithelia affected by aminoglycosides.     

Detection of YMDD motif mutants by oligonucleotide chips in lamivudine-untreated patients with chronic hepatitis B virus infection

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.     

Alveolar type II cell abnormalities and peroxide formation in lungs of rats given IL-1 intratracheally

Acute lung injury (ALI) is characterized by increased lung levels of proinflammatory cytokines, inflammation, oxidative stress, edema, and impaired gas exchange. Notably, ALI patients also exhibit pulmonary surfactant abnormalities, including increased levels of phospholipids in their lung lavages. In the present study, to assess early alterations of the lung surfactant system in ALI, we induced inflammation and acute lung injury in rats by administering interleukin-1 (IL-1) intratracheally. Five h after IL-1 instillation, we examined lung tissue ultrastructure by electron microscopy using both routine staining methods and cerium chloride staining to localize hydrogen peroxide (H₂O₂) histologically. We also measured lung lavage phospholipid levels, lung tissue -glutamyl transpeptidase (GGT) activities (a marker of oxidative stress), and arterial blood oxygen tensions. We observed that lungs of rats given IL-1 intratracheally had increased neutrophil accumulation, increased H₂O₂ production, and increased alveolar type II (ATII) pneumocyte ultrastructural abnormalities compared to rats given saline intratracheally. Intratracheal instillation of IL-1 also increased phospholipid levels in the bronchoalveolar lavage (BAL), possibly as a consequence of the abnormal discharge of lamellar bodies into the alveolar lumen. In addition, IL-1-insufflated rats had increased lung GGT levels and impaired blood oxygenation compared to saline-insufflated rats. Treatment with mepacrine decreased lung neutrophil accumulation, ultrastructural lung abnormalities, lung lavage phospholipid levels, lung tissue GGT levels, and blood oxygenation impairment in rats given IL-1 intratracheally, suggesting a possible relationship between these events. Our results indicate that IL-1-induced acute lung injury in rats is marked by neutrophil-dependent oxidative stress, ATII cell defects, abnormal discharge of lamellar body phospholipids, and impaired blood oxygenation.     

Relationship between normal heart size and body indices in Korean

We provided a curve-fit equation to predict the normal heart weight (g) in Koreans by examining 422 autopsies (215 males and 207 females, from newborn to age 77 yr) who were relatively in good general condition. Heart weight was well correlated with body surface area (m2), body weight (kg), and body height (cm) but poorly with age in both sex. Heart weight progressively increased from birth to the earlier 3rd and 4th decades in male and female, respectively, and then gradually decreased; mean heart weight of all age group was greater in male than in female and significantly different from birth to 4th decade. In both sex, heart weight exponentially increased in accordance with the increase of body height, body weight, and body surface (in male, heart weight=0.00312 x body height(2.239), r2=0.750, p<0.0001; in female, heart weight=0.00443 x body height(2170), r2=0.781, p<0.0001; in male, heart weight=9.22 x body weight(0.853), r2=0.770, p<0.0001; in female, heart weight=9.00 x body weight0.855, r2=0.820, p<0.0001; in male, heart weight=155.18 x body surface area1.290, r=0.808, p<0.0001; in female, heart weight=124.13 x body surface area1.242, r=0.834, p<0.0001). These results indicate that heart weight is better correlated with body surface area than with body weight; however, body weight should be a better determinant of a predicted heart weight, since body surface area is entirely dependent on body height and body weight.     

Mutational analysis of Fas ligand gene in human non-Hodgkin lymphoma

Among the systems triggering apoptosis, the Fas-Fas ligand (FasL) system is recognized as a major pathway for the induction of apoptosis in cells and tissues. Ligation of Fas by either an agonistic antibody or FasL transmits a 'death signal' to the target cell, potentially triggering apoptosis. Alterations of genes along the Fas-mediated apoptosis pathway have been reported in many human cancers. However, there have been no data regarding FasL gene mutations in human cancers. We hypothesized that FasL gene mutation might be involved in the development of non-Hodgkin lymphoma (NHL). In this study, we analyzed the entire coding region of the FasL gene for the detection of somatic mutations in a series of 111 NHLs and found that one tumor had a FasL gene mutation in the cytoplasmic domain. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant in 293T cells, but couldn't find any significant loss of cell death compared to the wild-type FasL. Together, these data suggest that FasL is occasionally mutated in human NHL and that FasL mutations appear to play no role in the pathogenesis of the vast majority of NHLs.     

Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis

Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.     

Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease: A Multicenter,Randomized, Phase IV Clinical Trial

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. {"type":"clinical-trial","attrs":{"text":"NCT02681952","term_id":"NCT02681952"}}NCT02681952).     

The effects of total sleep deprivation on brain functional organization: mutual information analysis of waking human EEG.

Sleep deprivation can affect the waking electroencephalogram (EEG) that may reflect functional organization of the brain. We examined the effect of total sleep deprivation (TSD) on functional organization between different cortical areas from the waking EEG. Waking EEG data were recorded from 18 healthy male volunteers with eyes closed after 8-h night's sleep and after 24 h of TSD. The averaged cross mutual information (A-CMI) after 24 h of TSD were compared to before TSD. 24 h of TSD yielded the decreased A-CMIs in the inter-hemispheric C3-F4, C3-F8, and C3-C4 pairs: therefore, the electrodes that contribute to pairs with significant decrease of A-CMI were C3, F4, F8, and C4. The decreased A-CMIs between C3 and right frontal and central brain areas after 24 h of TSD may reflect the changes of cortico-cortical functional organization by homeostatic process during TSD. Our results of the frontal-area-related A-CMI decreases may support that the frontal brain regions are related to the homeostatic deterioration of brain function due to TSD.     

Anti-angiogenic effects of Hypericin-photodynamic therapy in combination with Celebrex in the treatment of human nasopharyngeal carcinoma

Photodynamic therapy (PDT) is being investigated as an alternative treatment modality in cancer treatment. It has been shown to induce tumor hypoxia and upregulation of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The objective of this study was to improve in vivo tumor growth control of nasopharyngeal carcinoma (NPC), treated at a subcurative dosage by using a combination of Hypericin-PDT and COX-2 inhibitor, Celebrex (CX). The effect of an initial CX dose at 6- and 24-h post-PDT was investigated simultaneously. It was observed that hypoxic NPC/CNE2 cells upregulate both COX-2 and VEGF A genes in vitro. In vivo studies, down-regulation of COX-2 and hypoxia inducible factor-1alpha (HIF-1alpha) genes at 24-h post-PDT and bulk tumor ablation at 48-h post-PDT was observed. However, 24-28 days later regrowth was observed. In a combination treatment, 1st CX dose at 6-h post-PDT had the highest tumor control in which tumors were 相似文献   

Immunization with Combined HSV-2 Glycoproteins B2:D2 Gene DNAs: Protection against Lethal Intravaginal Challenges in Mice

The immunity of a combined DNA vaccine of HSV-2 glycoproteins B2 (gB2) and D2 (gD2) genes in comparison to individual vaccines was studied with regard to protecting against the HSV infection. Two recombinant DNA vaccines of the pHS2-gB2 or pHS2-gD2 were constructed and formulated. The neutralizing antibody titers appeared higher in the B2:D2 gene cocktail-vaccinated mice than that of the individual B2 or D2 gene-vaccinated group alone, and the positive KOS control induced higher titer of the neutralizing antibody than combined or individual gene vaccines. The mock-immunized mice failed to induce enough. The ranks for the CTL activity and the protection rates against the lethal intravaginal challenge were shown as KOS>B2:D2 cocktail>D2>B2 gene vaccines. The vaginal external diseases in the B2:D2 or D-vaccinated mice were significantly reduced against the challenging dosages. The virus titers in the vaginal secretions of the vaccinated mice significantly reduced with time, and the B2:D2 gene vaccine decreased more than each individual vaccine alone. It can be concluded that the cocktailed vaccines are more effective in the humoral and cellular immune responses in the mice, and in the protection of the mice against the intravaginal challenging dosages when compared with individual gene vaccines. All the DNA vaccines failed to block the latent infection in sensory nerves.