Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

Effects of sub-toxic concentrations of camphorquinone on cell lipid metabolism

The biological effects of camphorquinone (CQ), an initiator for light-polymerized resins, have been reported to relate to its ability to generate free radicals and cause radical-induced membrane damage via lipid peroxidation. However, the effects of CQ on lipids other than peroxidation may result in unfavorable tissue responses especially at concentrations that are not overtly toxic to cells. The purpose of the current study was to examine the effects of CQ on cell lipid metabolism at subtoxic concentrations, with or without visible light irradiation. HCP and THP-1 cells were exposed to CQ with or without light irradiation under clinically relevant conditions and lipid metabolism was analyzed using 14C-labeling and thin-layer chromatography. We found that CQ increased synthesis of neutral lipids, such as triglycerides, from 7 to nearly 15% of the total and diglycerides from 2% to about 3% of the total in HCP cells, while synthesis of phospholipids, such as sphingomyelin, was decreased by 1-1.5%. In THP-1 cells cholesterol synthesis increased more than 2-fold and cholesterol ester synthesis increased more than 5-fold. Light-activated CQ did not differ significantly in terms of its bioactivity compared to no-light conditions. We conclude that CQ significantly altered the metabolism of several important structural lipids in two cell types at sub-toxic concentrations that are clinically relevant. These changes in lipid metabolism may in turn affect membrane integrity and permeability and possibly lead to significant changes in cell responses.     

Mercury (II) alters mitochondrial activity of monocytes at sublethal doses via oxidative stress mechanisms

The perennial controversy about the safety of mercury in dental amalgams has adversely affected the availability and the quality of dental care. Chronic Hg(II) blood concentrations above 300 nM are known to alter function of the nervous system and the kidney. However, the effects of blood concentrations of 10 to 75 nM, far more common in the general population, are not clear and mechanisms of any effects are not known. The monocyte is an important potential target of Hg(II) because of its critical role in directing inflammatory and immune responses. In the current study we tested the hypothesis that concentrations of Hg(II) of 10 to 300 nM alter monocyte activity via a redox-dependent mechanism. Mitochondrial activity was used to establish inhibitory concentrations of Hg(II) following 6 to 72 h of exposures to THP1 human monocytic cells. Then subinhibitory concentrations were applied, and total glutathione levels and reactive oxygen species (ROS) were measured. Antioxidants [N-acetyl cysteine, (NAC); Na2SeO3, (Se)] and a pro-oxidant (tert-butylhydroquinone, tBHQ) were used to support the hypothesis that Hg(II) effects were redox-mediated. After 72 h of exposure, 20 microM of Hg(II) inhibited monocytic mitochondrial activity by 50%. NAC mitigated Hg(II)-induced mitochondrial suppression only at concentrations of greater than 10 microM, but Se had few effects on Hg-induced mitochondrial responses. tBHQ significantly enhanced mitochondrial suppression at higher Hg(II) concentrations. Hg(II) concentrations of 75 and 300 nM (0.075 and 0.30 microM, respectively) significantly increased total glutathione levels, and NAC mitigated these increases. Se plus Hg(II) significantly elevated Hg-induced total cellular glutathione levels. Increased ROS levels were not detected in monocytes exposed to mercury. Hg(II) acts in monocytic cells, at least in part, through redox-mediated mechanisms at concentrations below those commonly associated with chronic mercury toxicity, but commonly occurring in the blood of some dental patients.     

痛

黑暗!黑暗!!黑暗!!!这样的世界看不到半点光明。孤独的舞者终究还是孤独地倒下,然后又孤独地消失。黑暗呀,为什么老是缠绕着我?一声“妈妈”划破了天际,却也突不出黑暗的包围。谁来应我一声呀,妈妈,你在哪里呀?我的心在不停地挣扎,告诉自己:“不怕,不怕。”可这是在黑暗里呀,周     

Heat-inactivated frog virus 3 selectively inhibits equine herpesvirus type 1 translation in a temporal class-dependent manner

Superinfection of equine herpesvirus type 1 (EHV-1)-infected rabbit kidney cells with heat-inactivated frog virus 3 (delta FV3) differentially blocked EHV-1 protein synthesis. The extent of inhibition varied with the specific EHV-1 message, but in general late protein synthesis was inhibited more than early and immediate early translation. Since FV3 has been shown to block heterologous RNA and protein synthesis, it was necessary to determine whether the observed reduction in herpesvirus protein synthesis was primarily due to a block in translation or to an earlier inhibition of EHV-1 mRNA synthesis. To distinguish between these alternatives, replicate cultures of EHV-1 infected cells were either superinfected with delta FV3 or treated with 10 micrograms/ml actinomycin D at 6 hr after infection, and EHV-1 protein synthesis monitored 3 hr later. We found that addition of actinomycin D to EHV-1 infected cultures had only a slight effect on EHV-1 translation, whereas superinfection with delta FV3 markedly reduced EHV-1 protein synthesis. This result suggested that the observed decline in EHV-1 protein synthesis was not due to the inhibition of herpesvirus mRNA synthesis. In addition, we showed that RNA extracted from delta FV3-superinfected cells directed the synthesis of full-size EHV-1 proteins in vitro indicating that shut-off was not caused by the degradation of EHV-1 mRNAs. Taken together these results show that delta FV3 selectively inhibited EHV-1 protein synthesis and are consistent with earlier observations which suggest that translational shut-off occurs at initiation.     

Equine herpesvirus type 1 infected cell polypeptides: evidence for immediate early/early/late regulation of viral gene expression

EHV-1 polypeptide synthesis was examined in productively infected rabbit kidney and hamster embryo cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses of extracts from [35S]methionine- and 3H-amino acid-labeled-infected and mock-infected cultures revealed the presence of 30 infected cell-specific polypeptides (ICPs) which ranged in apparent molecular weights from 16.5K to 213K. Twenty-two of these ICPs comigrated with virion structural proteins. Four ICPs (203K, 176K, 151K, 129K) were detected in extracts of infected cultures labeled in the presence or absence of actinomycin D (Act D) immediately after release from a 4-hr treatment with cycloheximide (CH). These polypeptides, which were designated as EHV-1 immediate early (alpha) ICPs, were not detected in unblocked (non-CH-treated) infected cells. The most abundant ICP was a 31.5K nonstructural protein which, in addition to a 74K protein, was detected in unblocked infected cells at 2-3 hr postinfection. These proteins appeared to be regulated as early (beta) ICPs, since neither protein was observed in Act D-treated cultures released from CH block. Twelve ICPs were classified as late (gamma) polypeptides on the basis of their reduced synthesis in cultures in which viral DNA replication was inhibited by phosphonoacetic acid. All but one (40K) of these late ICPs corresponded to virion structural proteins.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.