[Collateral circulation compensation mode in patients with severe bilateral internal carotid artery stenosis/occlusion].

Objective: To investigate the correlation between collateral flow compensation mode and interventional treatment decision in patients with severe bilateral internal carotid artery stenosis/occlusion. Methods: According to the location of internal carotid artery lesions, patients with severe stenosis/occlusion of bilateral internal carotid artery were selected at the Second Affiliated Hospital, Qiqihar Medical University and the Sixth Medical Center of PLA General Hospital from May 2017 to June 2020. Results: A total of 42 patients were finally enrolled and divided into 4 types, including 34 males and 8 females with median age 61±8(48-82)years. The collateral circulation pathways manifested as following modes: anterior communicating artery collateral, posterior communicating artery collateral, ophthalmic artery collateral, posterior cerebral middle cerebral artery pial anastomosis collateral, posterior choroidal artery anterior choroidal artery collateral, external carotid internal carotid artery C4 segment collateral, pericallosal artery anastomosis collateral, dural and pial collateral and neovascularization. Type Ⅰ severe stenosis/occlusion of C1 segment was found in 20 cases (47.6%). There were 5 cases (11.9%) of type Ⅱ severe stenosis/occlusion from C2 to C6 prior to ophthalmic artery branch. Type Ⅲ severe stenosis/occlusion occurred in 2 cases (4.8%) after the split of ophthalmic artery. Type Ⅳ was mixed type in 15 cases (35.7%). Conclusions: The compensatory pathway of collateral circulation is closely related to the lesion location. To explore the compensatory pattern of collateral circulation is helpful for clinicians to accurately analyze the lesion characteristics and guide individualized interventional therapy.

[Association of thallium exposure during pregnancy with maternal blood pressure and hypertensive disorder complicating pregnancy].

Objective: To investigate the association of thallium exposure during pregnancy with pregnant blood pressure changing and hypertensive disorder complicating pregnancy(HDCP). Methods: A total of 3 240 pregnant women who had establish maternal health care manual in Ma'anshan Maternal and Child Health-Care Hospital and met the inclusion and exclusion criteria were included in this study between May 2013 and September 2014.We collected their general demographic characteristics and blood pressure through questionnaire and medical records. Meanwhile we measured serum thallium concentrations by experimental technology. We use multiple logistic regression to analyze the association between thallium exposure during pregnancy and HDCP. Mixed linear model were used to analyze the association between thallium concentration and maternal systolic blood pressure (SBP) or diastolic blood pressure(DBP) in different trimesters Results: The age of 3 240 pregnant woman was (26.61±3.64) years, and the detection rate of HDCP was 5.9%(191).The median (P25, P75) of thallium concentrations in first trimester, second trimester and third trimester were 62.96 (50.79, 77.04), 62.19 (50.87, 75.26), 48.84 (38.00, 66.00) ng/L, respectively. Multiple logistic regression results suggested after adjusting various confounding factors, the risk of HDCP in pregnant women with high concentrations of thallium (>77.04 ng/L) in the first trimester is 1.75 (95%CI:1.01-3.03) times higher than which with low concentrations(<50.82 ng/L). Mixed linear model results suggested there are positive correlation between thallium concentrations with maternal DBP in first trimester (ß=1.12, 95%CI: 0.39-1.85). Conclusion: Exposure to high levels of thallium during first trimester may increase the risk of HDCP, and the exposure of thallium may be effective to DBP of pregnant.

[Adverse maternal and infant health effects caused by thallium exposure during pregnancy].

Thallium is a highly toxic heavy metal. The adverse maternal and infant health effects caused by thallium exposure during pregnancy have also attracted more and more scholars' attention. This study focused on the sources of thallium exposure and its influencing factors, the association between thallium exposure during pregnancy and pregnancy complications and adverse birth outcomes in newborns, the effects of thallium exposure during pregnancy on children's growth and development after birth. In terms of potential mechanisms, the related research progress was reviewed in this study, which could provide a new basis for further research on the harm, prevention and control of thallium exposure during pregnancy.

[The relationship of maternal and umbilical cord blood zinc level associated with newborn birth weight: a birth cohort study].

Objective: To study serum zinc level in pregnancy and umbilical cord blood and their association with newborn birth weight. Methods: Pregnant women accepting obstetric examination in Ma'anshan Maternal and Child Care Center were recruited from May 2013 to September 2014. The follow up was conducted during their first, second and third trimesters of pregnancy and the self-designed questionnaire was used to collect information of social and demographic characteristics. Blood samples in the first, second pregnancy period and umbilical cord blood samples were collected and serum concentrations of zinc were assayed. 3 239 mother-infant entered the final analysis. We divided serum zinc level into low (P(75)) groups according to their exposure concentrations at each trimesters. Non-conditional multivariate logistic regression model was conducted to evaluate the association between serum zinc level in first, second trimesters of pregnancy and umbilical cord blood with small for gestational age (SGA) and large for gestational age (LGA). Results: Serum zinc level in P(50) (P(25)-P(75)) during the first, second trimesters and cord blood were 1 016.18 (907.09-1 145.60), 813.36 (732.47-897.89) and 903.44 (808.71-1 015.64) µg/L, respectively. The prevalence of zinc deficiency during the first, second trimesters and cord blood were 1.5% (44/2 957), 15.9% (492/3 087) and 6.5% (176/2 707), respectively. The prevalence of total SGA and LGA were 9.7% (313/3 239) and 16.5% (536/3 239), respectively. Compared to high-level serum zinc group, the risk of SGA (OR (95%CI) in low-level serum zinc group during first trimesters was 1.51 (1.05-2.19)). Serum zinc level among second pregnancy period and umbilical cord blood had no statistically significant effect on SGA and LGA (both P values >0.05). Conclusion: Zinc nutritional status of pregnant women in Ma'anshan city was at a good level. The low serum zinc level in first trimester increased the risk of SGA.

Predictive factors for inadequate colon preparation before colonoscopy.

BACKGROUND: It could be helpful to ascertain which patients are at risk of poor bowel preparation prior to performing sedated colonoscopy. The aim of the present study was to identify the predictive factors for poor colon preparation prior to colonoscopy. METHODS: A prospective study was performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient characteristics, food consumed within 2 days of colonoscopy, volume of polyethylene glycol (PEG) solution, interval between completing PEG and examination, number of bowel movements, and character of the last stool were evaluated. RESULTS: Seven hundred and three patients were enrolled (mean age 50.3 ± 11.6 years, 43 % female). In univariate analysis, character of the last stool (<0.001), body weight (p = 0.007), body mass index (p = 0.047), waist circumference (p = 0.008), buttock girth (p = 0.016), meal residue score (<0.001), and interval between end of PEG and colonoscopy (p = 0.01) were related to inadequate colon preparation. In multivariate analysis, waist circumference (p < 0.001), meal residue score (p < 0.001), and characteristics of last stool (p < 0.001) were variables that predicted poor colon preparation. CONCLUSIONS: Patients who have consumed a high residue diet and/or who report that their last stool is semisolid are likely to have poor bowel preparation, and consideration could be given to rescheduling the examination.

Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy.

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity-determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin-28B (IL-28B) locus affect the outcome of interferon (IFN)-based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response-guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV-1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non-EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts≥15×10(4) /µL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.

[Study on the relationship of thallium exposure and outcomes of births].

Objective: To investigate the relationship of thallium exposure and outcomes of births. Methods: A total of 3 236 mothers who had visited in Ma'anshan Maternal and Child Health-Care Hospital between May 2013 and September 2014 were included in this study and their thallium concentrations measured from samples of maternal and umbilical cord blood by inductively coupled plasma mass spectrometry. The results were correlated and evaluated with birth outcomes of the infants, using the multiple linear regression method. Results: The median (P(25)-P(75)) of thallium levels in first trimester, second trimester and umbilical cord blood were 61.7 (50.8-77.0), 60.3 (50.8-75.2) and 38.5 (33.6-44.1) ng/L, respectively. After adjustment for potential confounders, the thallium levels showed an inversely significant association with birth head circumference (unstandardized ß coefficient=-0.41, 95%CI: -0.76- -0.06) in the first trimester blood, and associated with reduced birth length (unstandardized ß coefficient=-0.65, 95%CI: -1.25- -0.05) in umbilical cord blood. However, there appeared no significantly associations with birth weight, length and head circumference (P>0.05) in second trimester. On stratification by sex, in girls but not in boys, the thallium levels were adversely associated with birth head circumference (unstandardized ß coefficient=-0.53, 95%CI: -1.05--0.01) in the first trimester and were associated with decreased birth weight (unstandardized ß coefficient=-277.08, 95%CI: -485.13- -69.03) and length (unstandardized ß coefficient=-1.39, 95%CI: -2.26- -0.53) in umbilical cord blood thallium. Conclusions: Thallium exposure appeared a gender difference in newborn birth outcomes. In the first trimester, it was negatively associated with the birth head circumference, in the umbilical cord blood, and reduced birth weight and length in girls.

Sweet hyperopia: refractive changes in acute hyperglycemia.

PURPOSE: A prospective study was performed to evaluate refractive and ocular biometric changes in acute hyperglycemic status in patients with diabetes mellitus. METHODS: From January to August 2002, 48 eyes of 24 patients with persistent diabetes and a plasma glucose level>or=17 mmol/L or HbA1c>or=10.0% on admission were enrolled in this prospective study. Upon admission to Tri-Service General Hospital in Taipei, Taiwan, these patients underwent intensive glycemic control. The basic ophthalmic examinations, including visual acuity, intraocular pressure measurement, slit lamp, and fundus examinations, were conducted. The ocular parameters including refraction, anterior chamber depth, lens thickness, axial length, mean keratometry, and thinnest corneal thickness were evaluated by A-mode scan and Orbscan II. Each patient underwent clinical follow-up visits at 1, 2, and 4 weeks after the acute hyperglycemic episode. RESULTS: Of the 24 patients, 18 were male and 6 were female. The mean age of the patients was 55 years (range: 38 to 69). Comparing the refractive status on admission and at week 4, the authors found that 8 cases (16 eyes, 33%) showed hyperopia during hyperglycemia (+1.9+/-0.8 D), but in the other 16 cases (32 eyes, 67%), there were no significant changes. In addition, there were also no significant changes in anterior chamber depth, lens thickness, axial length, thinnest corneal thickness, or mean keratometry in the follow-up period. CONCLUSIONS: Transitory hyperglycemia produces hyperopia. The alteration in refractive index in the lens may contribute to the hyperopic change, but no change of ocular biometrics in lens or cornea is observed.

Production and characterization of monoclonal antibodies that localize human thymidylate synthase in the cytoplasm of human cells and tissue.

Thymidylate synthase (TS; EC 2.1.1.45) is an important cellular enzyme that converts dUMP to dTMP, which is essential for DNA biosynthesis. In addition, TS is an important cellular target for the fluoropyrimidine cytotoxic drugs that are widely used in the treatment of solid tumors. We have generated five monoclonal antibodies against human TS using a recombinant human TS enzyme. These antibodies react specifically with human TS and display negligible cross-reactivity with other cellular proteins found in human cells. Binding affinity studies demonstrate that all antibodies form a tight interaction with recombinant human TS enzyme (Kd range = 0.3-11.0 nM). All antibodies display reactivity on enzyme-linked immunosorbent assay and immunoprecipitation. On Western blot analysis each detects a protein of approximately 36 kDa molecular mass under denaturing conditions. In addition to their reactivity on immunoprecipitation and Western analysis, two of the antibodies, TS 106 and TS 109, are reactive on immunohistochemical staining of human colon carcinoma cell lines and tissue, producing a granular cytoplasmic staining pattern. Specificity for TS is demonstrated by the lack of staining with preimmune IgG and the disappearance of the signal when the antibodies are preabsorbed with recombinant human TS enzyme. Quantitation of TS by Western blot analysis and biochemical FdUMP binding assay in 5-fluorouracil-resistant colon carcinoma cell lines (NCI H630R10, NCI H630R1) and a sensitive colon carcinoma cell line (NCI H630) revealed a 36- and 6-fold increase in TS in the resistant cell line as measured by the biochemical assay compared to a 39- and 10.6-fold increase as measured by densitometric analysis of the Western blot. These comparative studies of immunohistochemical, Western, and biochemical analyses reveal that the immunological detection of TS in human colon cell lines is a sensitive and quantitative assay. Thus the ability of these antibodies to detect TS in human cancer cells and tissue may allow measurement of TS in human tissues by quantitative immunohistochemistry in studies of drug resistance and for determination of proliferative rates.

Isolation and identification of a small molecular weight inhibitor of cyclic nucleotide phosphodiesterase from bovine brain.

In a search for endogenous regulators for cyclic nucleotide phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), we found that the ultrafiltrate of bovine brain homogenate contained a cyclic nucleotide phosphodiesterase inhibitor. The inhibitor-containing fraction was further purified by ion-exchange column chromatography and gel filtration chromatography. The purified inhibitor was found to be a small molecular weight compound which had a maximum absorption at 248 nm. This compound was identified by thin-layer chromatography and high-pressure liquid chromatography as hypoxanthine. We suggest that hypoxanthine may serve as an endogenous regulator for the hydrolysis of cyclic nucleotide by cyclic nucleotide phosphodiesterase.

Identification of the hematopoietic growth factors elaborated by bone marrow stromal cells using antibody neutralization analysis.

These studies were undertaken to characterize the subclasses of hematopoietic growth factors produced by stromal cells in long-term murine bone marrow cultures. Exposure of these cultures to extremely high doses of irradiation (500 Gy), followed by endotoxin stimulation, permitted detection and characterization of various growth factor activities in the unconcentrated conditioned medium. To determine the nature of these activities, neutralization studies were performed using antisera against the following subclasses of purified colony-stimulating factors (CSFs): purified L-cell CSF-1, recombinant granulocyte-macrophage CSF (rGM-CSF), and recombinant interleukin 3 (rIL3). The antiserum against CSF-1 consistently abrogated 100% of the CSF bioactivity in irradiated stromal cell-conditioned medium (CM) but was only capable of neutralizing 62%-91% of the bioactivity in endotoxin-stimulated, irradiated stromal cell-CM. Antisera against rGM-CSF and rIL3 demonstrated variable effects. When the antisera were used in combinations, only the mixture of anti-CSF-1 + anti-GM-CSF resulted in 100% neutralization of the activities in endotoxin-stimulated, irradiated stromal cell-CM. This CM stimulated the IL3/GM-CSF-responsive cell line FDC-P1 but not the IL3-responsive (GM-CSF-unresponsive) cell line 32D cl-23. The FDC-P1 growth-promoting activity was inhibited only by the antiserum against GM-CSF and not by antiserum against IL3. These experiments indicate that stromal cells from long-term bone marrow cultures can produce and release CSF-1 and GM-CSF while the production of IL3 in this system, if there is any, could not be demonstrated.

Note: Decoupling design for high frequency piezoelectric ultrasonic transducers with their clamping connections.

This work presents the flexure-mechanism based decoupling design between high frequency piezoelectric ultrasonic transducers and their clamping connections to improve ultrasonic energy transmission efficiency. The ring, prismatic beam, and circular notched hinge based flanges were presented, and the crucial geometric dimensions of the transducers with the flexure decoupling flanges were determined. Finite element analysis (FEA) was carried out to investigate the dynamic characteristics of the transducers. Finally, experiments were conducted to examine and verify the effects of the proposed decoupling flanges. FEA and experimental results show that smaller frequency deviations and larger tip displacement amplitudes have been achieved by using the transducers with the flexure flanges compared with the transducer with a rigid ring-type flange, and thus the ultrasonic transmission efficiency can be improved through the flexure flanges.

Intracellular distribution of the endogenous and transfected beta form of thyroid hormone nuclear receptor visualized by the use of domain-specific monoclonal antibodies.

To study the regulation, tissue distribution, and subcellular localization of nuclear receptor for thyroid hormone, monoclonal antibodies (mAbs) against the human placental c-erbA (hTR beta 1) protein were prepared. hTR beta 1 was expressed in Escherichia coli and purified to apparent homogeneity. The purified hTR beta 1 was used to produce monoclonal antibodies. Three hybridomas, secreting mAb J51, J52, and J53, were isolated. All of these mAbs recognized hTR beta 1. J51 and J52 belong to the immunoglobulin G1-k subclass; J53 is an IgM. To evaluate cross-reactivity with other classes of c-erbAs, the three mAbs were used to immunoprecipitate the in vitro translation products of human (h) TR alpha 1, TR alpha 2, rat (r) TR beta 1, TR alpha 1, and TR alpha 2. None of these three mAbs reacted with h- or rTR alpha 1 and TR alpha 2. J51 did not react with rTR beta 1, but J52 and J53 cross-reacted with rTR beta 1 with the same activity as hTR beta 1. To localize the epitopes in the hTR beta 1 molecule, [35S]methionine-labeled and truncated hTR beta 1 containing the hormone-binding domain E (Lys235-Asp456; Lys201-Pro414), domain D (Met169-Asp456), or the DNA-binding domain C (Glu100-Asp456) were expressed in E. coli and purified. Immunoprecipitation of the above truncated hTR beta 1 with mAbs indicated that the epitopes for J51 and J52 were located in two different sites in the A/B domain. The epitope for J53 was located in the E domain. Using immunocytochemistry and mAb J52, the endogenous TR beta 1 in rat pituitary GH3 cells was visualized to be exclusively present in nuclei. The transfected hTR beta 1 in monkey COS-1 and human choriocarcinoma JEG-3 cells was recognized by both J51 and J52. Interestingly, the intracellular localization of the transfected hTR beta 1 or rTR beta 1 in the above two cell lines depended on the level of expression. TR beta 1 expressed at low levels was found exclusively in nuclei. However, for high level expression of TR beta 1, cytoplasmic localization was also detected. J53, however, failed to detect nuclear fluorescence of the endogenous and transfected TR beta 1 in fixed cells, suggesting that its antigenic site might be occluded. Localization of the endogenous and transfected TR beta 1 in nuclei indicated that these two receptor proteins are structurally indistinguishable.(ABSTRACT TRUNCATED AT 400 WORDS)

Monoclonal antibodies to lipocortin-1 as probes for biological function.

We have developed two monoclonal antibodies to human lipocortin-1 (103 and 105) as reagents for quantitating the protein in biological systems and neutralizing its activity. Lipo 105 is a high affinity antibody that is functional in ELISA and Western blot formats. The antibody recognizes a site between amino acids 30 and 55 in the lipocortin-1 sequence and can be used on native or denatured protein. Lipo 103 is an antibody that neutralizes the phospholipase A2 inhibitory activity of lipocortin-1 by blocking binding of the protein to phospholipid surfaces. The antibody is specific for native human lipocortin-1. Lipo 103 was recently shown to block lipocortin-1-dependent differentiation of a squamous carcinoma cell line, demonstrating its usefulness as a probe for function.

Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts.

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the maintenance of the cellular redox balance. The biological effects of G6PD deficiency in nucleated cells were studied using G6PD-deficient human foreskin fibroblasts (HFF). In contrast to that of normal HFF, the doubling time of G6PD-deficient cells increased readily from population doubling level (PDL) 15 to 63. This was accompanied by a significant increase in the percentage of G(1) cells. The slow-down in growth preceded an early entry of these cells into a nondividing state reminiscent of cellular senescence. These cells exhibited a significant increase in level of senescence-associated beta-galactosidase (SA-beta-gal) staining. The importance of G6PD activity in cell growth was corroborated by the finding that ectopic expression of active G6PD in the deficient cells prevented their growth retardation and early onset of senescence. Mechanistically, the enhanced fluorescence in dichlorofluorescin (H(2)DCF)-stained G6PD-deficient cells suggests the possible involvement of reactive oxygen species in senescence. Taken together, our results show that G6PD deficiency predisposes human fibroblasts to retarded growth and accelerated cellular senescence. Moreover, G6PD-deficient HFF provides a useful model system for delineating the effects of redox alterations on cellular processes.

Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts.

Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in cellular redox homeostasis, which is crucial for cell survival. In the present study, we found that G6PD status determines the response of cells exposed to nitric oxide (NO) donor. Treatment with NO donor, sodium nitroprusside (SNP), caused apoptosis in G6PD-deficient human foreskin fibroblasts (HFF1), whereas it was growth stimulatory in the normal counterpart (HFF3). Such effects were abolished by NO scavengers like hemoglobin. Ectopic expression of G6PD in HFF1 cells switched the cellular response to NO from apoptosis to growth stimulation. Experiments with 1H-¿1,2,4oxadiazolo¿4, 3-aquinoxalin-1-one and 8-bromo-cGMP showed that the effects of NO on HFF1 and HFF3 cells were independent of cGMP signalling pathway. Intriguingly, trolox prevented the SNP-induced apoptosis in HFF1 cells. These data demonstrate that G6PD plays a critical role in regulation of cell growth and survival.

An anti-p24 monoclonal antibody shows cross-reactivity with multiple HIV-1 proteins.

We produced three murine monoclonal antibodies (mAbs) against the HIV-1 proteins. These three mAbs, namely CA-1, CA-2, CA-4, were IgG1 and all reacted with p24 on the HIV-1 Western blot. One of the mAbs, CA-4, also recognized p13, p21, p28, p29, p32, p39, p47, p55 on the Biotech/Du Pont HIV-1 Western blot strips and p21, p24, p28, p29, p39, p47, p55, p68, p80, p96; p110 on the Bio-Rad strips. CA-4 did not react with H-9 cell lysate nor with other retroviral antigens such as HTLV-1 or HIV-2 proteins. The binding of CA-4 to HIV-1 proteins was not blocked by deglycosylation. All three mAbs reacted with recombinant DNA derived capsid protein (p24) of HIV-1. These results suggest that many proteins in the HIV-1 Western blot contain antigenic epitope(s) similar to that of p24.

Raf activation by Ras and promotion of cellular metastasis require phosphorylation of prohibitin in the raft domain of the plasma membrane.

Prohibitin (PHB) is indispensable for Ras-induced Raf-1 activation, cell migration and growth; however, the exact role of PHB in the molecular pathogenesis of cancer metastasis remains largely unexamined. Here, we found a positive correlation between plasma membrane-associated PHB and the clinical stages of cancer. The level of PHB phosphorylated at threonine 258 (T258) and tyrosine 259 (Y259) in human cancer-cell membranes correlated with the invasiveness of cancer cells. Overexpression of phosphorylated PHB (phospho-PHB) in the lipid-raft domain of the cell membrane enhanced cell migration/invasion through PI3K/Akt and Raf-1/ERK activation. It also enhanced epithelial-mesenchymal transition, matrix metalloproteinase-2 activity and invasiveness of cancer cells in vitro. Immunoprecipitation analysis demonstrated that phospho-PHB associated with Raf-1, Akt and Ras in the membrane and was essential for the activation of Raf-1 signaling by Ras. Mice implanted with cancer cells stably overexpressing PHB in the plasma membrane showed enlarged cervical tumors, enhanced metastasis and shorter survival time compared with mice implanted with cancer cells without PHB overexpression. Dephosphorylation of PHB at T258 by site-directed mutagenesis diminished the in vitro and in vivo effects of PHB. These results suggest that increase in phospho-PHB T258 in the raft domain of the plasma membrane has a role in the Ras-driven activation of PI3K/Akt and Raf-1/ERK-signaling cascades and results in the promotion of cancer metastasis.

Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts.

PURPOSE: MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence. METHODS: This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated. RESULTS: This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni's test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively). CONCLUSIONS: The current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.

Intermediate outcomes of Ahmed glaucoma valve surgery in Asian patients with intractable glaucoma.

OBJECTIVE: To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) implantation in Asian patients with refractory glaucoma. METHODS: The study was a retrospective interventional case series conducted at a single institution between January 2004 and January 2006. The study population included 91 patients (91 eyes). RESULTS: A total of 70 patients were successfully treated (74.5%). Postoperatively, the median intraocular pressures declined significantly to 13 mm Hg (interquartile range: 10-20 mm Hg) on day 1 (P<0.001) and 17 mm Hg (interquartile range: 12-19 mm Hg) at the last follow-up examination (P<0.001). The cumulative probability of success according to Kaplan-Meier life-table analysis was 74% at 12 months and 43% at 2 years. Hazard of failure increased slightly with age, HR: 1.03 (95% confidence interval (CI)=1.00-1.05; P=0.044). The most common complication was hyphaemia at 12.77%. There were no serious complications involving loss of visual acuity or sight. CONCLUSIONS: AGV implantation is an acceptable treatment for refractory glaucoma in high-risk patients with few additional options.