Proteomics analysis of differentially expressed metastasis-associated proteins in adenoid cystic carcinoma cell lines of human salivary gland

Metastasis is the most insidious and life threatening aspect of cancers. However little is known about the molecular mechanisms of tumor metastasis. A poorly metastatic Acc-2 cell line and highly metastatic Acc-M cell line were selected as an experimental model to study on metastatic mechanisms and antimetastatic procedures. In the present study, two-dimensional gel electrophoresis and mass spectrometry are combined to approach the protein profiles associated with tumor metastasis between Acc-2 and Acc-M cell lines. Image analysis of silver stained 2-dimensional gels revealed that 12 protein spots showed significantly quantitative and qualitative variations and mass spectrometry is utilized to further identify these spots. Of the identified proteins, transketolase, Dim1p, v-Ha-ras oncogene, type I collagen pro alpha, tumor necrosis factor (ligand) superfamily member 4, and pirin etc, have shown associations with distinct aspect of tumor metastasis to some extent. The dissimilar expression patterns of these 12 spots indicate the different roles they may play involved in tumor metastasis.     

Vitamin D 依赖性佝偻病一例

患儿 ,女 ,2岁 8个月 ,因生长缓慢 2年入院。 2年前出现生长缓慢 ,身高较异卵双生的妹妹明显矮小 ,身高年增长率 <4cm/年。曾诊为“佝偻病” ,给与常规剂量的VitaminD和钙剂治疗效果不佳。近 3个月 ,患儿食欲明显减退 ,不食油腻 ,无吐泻。查体 :T 36 2℃ ,R 2 8次 /min ,P 98次 /min ,Bp90 / 6 0mmHg ,身高 77 5cm ,体重 9 5kg ,智力发育正常 ,语言发育正常 ,躯干与下肢比例正常 ,肋骨串珠 ,肋缘外翻 ,手镯、脚镯 ,轻度O型腿 ,步态轻度摇曳。心肺无异常 ,腹平软 ,肝右肋下 2cm ,脾不大。神经系统检查正常。实验室检查 :X线片示骨龄延迟…     

Adolescents' contraceptive use and pregnancy history: is there a pattern?

OBJECTIVE: To examine the association between pregnancy experience and adolescents' contraceptive use. METHODS: We conducted a retrospective study of 920 sexually active adolescents not desiring pregnancy. Adjusted multivariable logistic regression analyses were used to assess the explanatory value of previous birth and abortion as well as first pregnancy at presentation on contraceptive practice. RESULTS: Twenty-seven percent of the adolescents had been pregnant. Regardless of pregnancy history, 52% of adolescents used noneffective contraception (ie, condoms inconsistently or no method). Adolescents with previous abortion were three times (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.6, 7.3) more likely than never-pregnant adolescents to use hormonal contraception. However, although more likely to use contraceptive injections or implants, adolescent mothers were not more likely than never-pregnant adolescents to use oral contraceptives. Adolescents with prior abortion or birth were less than half (ORs 0.3 and 0.4, 95% CIs 0.2, 0.5 and 0.2, 0.6, respectively) as likely as never-pregnant adolescents to use condoms consistently. CONCLUSION: Previous pregnancy is associated with increased likelihood to use hormonal methods; however, a significant proportion of adolescents use noneffective methods and, thus, are at risk for repeat teenage pregnancies.     

Validity of information on comorbidity derived rom ICD-9-CCM administrative data

BACKGROUND: The comorbidity variables that constitute the Charlson index are widely used in health care research using administrative data. However, little is known about the validity of administrative data in these comorbidities. The agreement between administrative hospital discharge data and chart data for the recording of information on comorbidity was evaluated. The predictive ability of comorbidity information in the two data sets for predicting in-hospital mortality was also compared. METHODS: One thousand two hundred administrative hospital discharge records were randomly selected in the region of Calgary, Alberta, Canada in 1996 and used a published coding algorithm to define the 17 comorbidities that constitute the Charlson index. Corresponding patient charts for the selected records were reviewed as the "criterion standard" against which validity of the administrative data were judged. RESULTS: Compared with the chart data, administrative data had a lower prevalence in 10 comorbidities, a higher prevalence in 3 and a similar prevalence in 4. The kappa values ranged from a high of 0.87 to a low of 0.34; agreement was therefore near perfect for one variable, substantial for six, moderate for nine, and only fair for one variable. For the Charlson index score ranging from 0 to 5 to 6 or higher, agreement was moderate to substantial (kappa = 0.56, weighted kappa = 0.71). When 16 Charlson comorbidities from administrative data were used to predict in-hospital mortality, 10 comorbidities and the index scores defined using administrative data yielded odds ratios that were similar to those derived from chart data. The remaining six comorbidities yielded odds ratios that were quite different from those derived from chart data. CONCLUSIONS: Administrative data generally agree with patient chart data for recording of comorbidities although comorbidities tend to be under-reported in administrative data. The ability to predict in-hospital mortality is less reliable for some of the individual comorbidities than it is for the summarized Charlson index scores in administrative data.     

Use of an N-terminal half truncated IE1 as an antagonist of IE1, an essential regulatory protein in baculovirus

An immediate-early gene product of baculovirus, IE1, is essential for viral gene expression and for viral DNA replication. It has been demonstrated for Autographa californica nuclear polyhedrosis virus (AcNPV) that the C-terminal region of IE1 is required for dimerization. And the acidic N-terminal region of IE1 has been identified as the activation domain. We constructed an N-terminal 267 amino acid (a.a.) truncated mutant of Bombyx mori nuclear polyhedrosis virus (BmNPV) IE1, which was defective as a transactivator of a viral early gene (p35) promoter. We then examined possible IE1 antagonistic functions of this defective IE1, IE1TN, in BmNPV-infected cells. A transient expression experiment demonstrated that IE1TN strongly repressed the activation of the hr5-dependent p35 promoter derived from BmNPV infection. In addition, DpnI assay elucidated an inhibitory effect of IE1TN on the hr5-dependent replication of plasmid in BmN cells induced by NPV infection. A marked reduction in the production of virus was observed when the BmN cells were infected with BmNPV after transfection with IE1TN-expression plasmids. These results suggested that IE1TN could act as an IE1 antagonist in silkworm cells infected with BmNPV. We then analyzed the ability of IE1TN to inhibit the multiplication of BmNPV using transgenic silkworms. The BmNPV-resistance of the transgenic silkworms was very weak, suggesting insufficient expression of the transgene product, IE1TN.     

Could direct stenting reduce no-reflow in acute coronary syndromes? A randomized pilot study

Objectives Recently, direct stenting has been shown in retrospective and randomized studies to be feasible and safe in highly selected patients, with a potential interest to reduce the cost of the procedure and the rate of no-reflow. This randomized pilot study was designed to compare the incidence of no-reflow after direct stenting or conventional stenting after balloon predilation in acute coronary syndrome-related lesions. Methods and Results Between December 1998 and October 1999, 130 patients in our center with acute coronary syndromes were included in this study and randomized in 2 groups. In group A (n = 65), direct stent implantation was performed without balloon predilation. In group B (n = 65), conventional balloon predilation was carried out before stent implantation. Baseline clinical and angiographic characteristics before the procedure were similar in the 2 groups of patients. No-reflow was observed in 7.7% after direct stenting and in 6.1% after conventional stent implantation (P = not significant). The immediate clinical success rate was similar in the 2 groups. Among the procedural data, only duration of the procedure (shorter in the direct stenting group), the number of balloons used, and the quantity of contrast agent (lower in the direct stenting group) were significantly different between the 2 groups (P < .05). The 6-month clinical outcome was similar in the 2 groups. Conclusion This randomized study confirms the promising results of previous studies that show the feasibility and the safety of direct coronary stenting in highly selected acute coronary syndrome-related lesions. The major impact of this strategy is the improvement of the cost-benefit ratio, with no major influence on the acute complications and especially on the occurrence of no-reflow in this high-risk population. (Am Heart J 2002;143:1027-32.)     

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations

Background/Purpose: The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur.Methods: Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H & E and examined serially.Results: Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube.Conclusions: Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.     

Regulated expression of collagenases MMP-1, -8, and -13 and stromelysins MMP-3, -10, and -11 by human corneal epithelial cells

PURPOSE: This study investigated the regulated expression of collagenases (MMP-1, -8, and -13) and stromelysins (MMP-3, -10, and -11) by human corneal epithelial cells treated with IL-1 beta, TNF-alpha, and doxycycline, a medication used to treat ocular surface diseases. METHODS: Primary human corneal epithelial cell cultures were treated with IL-1 beta or TNF-alpha, with or without their corresponding inhibitors. Total RNA extracted from cells treated for 4 to 24 hours was subjected to semiquantitative RT-PCR and Northern hybridization. Conditioned media from 24-hour-treated cultures were evaluated for MMP production by ELISA and activity assays. RESULTS: Semiquantitative RT-PCR and Northern hybridization revealed that the mRNAs of MMP-1, -13, -3, -10, and -11 were dose dependently upregulated by IL-1 beta and TNF-alpha, whereas MMP-8 and -14 and tissue inhibitor of metalloproteinase (TIMP)-1 were not altered, in corneal epithelial cells. MMP ELISA and activity assays confirmed this dose-dependent increase in MMP-1, -13, -3, and -10 protein production in conditioned media by IL-1 beta and TNF-alpha. This stimulated production was inhibited by their neutralizing antibodies and by IL-1 receptor antagonist. Doxycycline suppressed stimulated MMP-1, -10, and -13 production at both the mRNA and protein levels. CONCLUSIONS: This study demonstrated that IL-1 beta and TNF-alpha upregulate collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, and -11) in human corneal epithelial cells. Doxycycline suppresses stimulated MMP-1, -13, and -10 at the mRNA and protein levels, which suggests that collagenases and stromelysins may play a role in the pathogenesis of sterile corneal ulceration and other ocular surface diseases.     

Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib

BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.     

Lung-heart weight ratio as a possible index of cardiopulmonary pathophysiology in drowning

The aim of the present study was to investigate the lung-heart weight ratio in fresh- and saltwater drowning (n=67 and n=75, respectively) as a possible index of cardiopulmonary pathophysiology, in comparison with acute myocardial infarction/ischemia (AMI, n=75) and asphyxiation (n=85). In drowning cases, the total value of the combined lung weight and the amount of pleural effusion was regarded as a possible total lung weight. The median value of the combined/total lung weight was the highest in saltwater drowning, which was followed by freshwater drowning, AMI and asphyxiation, showing a tendency to be mildly increased depending on the heart weight. The lung-heart weight ratio was significantly higher in fresh-/saltwater drownings (3.944+/-1.538 and 4.825+/-2.242, respectively) than in asphyxiation (2.846+/-1.042) and AMI (2.641+/-0.916) (P<0.0001), showing a tendency to be higher in saltwater than freshwater drowning. However, the value depended on the gender and age of the subjects, and the difference between freshwater drowning and asphyxiation was insignificant in females. These results suggested that the lung-heart weight ratio may be an index for investigating the influence of aspirated immersion medium in drownings.