Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.

Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma.

Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes. We found that as gliomas became more malignant, both CYP17A1 and DHEA were significantly upregulated in temozolomide (TMZ)-resistant cells and highly invasive cells. In particular, the increase of CYP17A1 was caused by Sp1-mediated DNA demethylation, whereby Sp1 competed with DNMT3a for binding to the CYP17A1 promoter in TMZ-resistant glioma cells. CYP17A1 was required for the development of glioma cell invasiveness and resistance to TMZ-induced cytotoxicity. In addition, DHEA markedly attenuated TMZ-induced DNA damage and apoptosis. Together, our results suggest that components of the Sp1-CYP17A1-DHEA axis, which promotes the development of TMZ resistance, may serve as potential biomarkers and therapeutic targets in recurrent glioma.

Mercury concentration and fish consumption in Taiwanese pregnant women.

OBJECTIVE: The aim of this study was to assess the relationship between fish consumption and total mercury concentration in maternal blood, umbilical cord blood, and placenta tissue of pregnant women in Taiwan. DESIGN: Cross-sectional study. SETTING: A medical centre in Taipei, Taiwan. SAMPLE: Sixty-five pregnant women delivered between July 2004 and March 2005. METHODS: We administered a questionnaire to each woman in the third trimester and collected blood samples and placenta tissue after delivery. Mercury concentrations in the maternal blood, cord blood and placenta tissue were measured using mercury analyser (Hiranuma HG-310, Hitachi, Japan). A dietitian calculated the quantity of fish consumed from the questionnaire. MAIN OUTCOME MEASURES: The total mercury concentration in maternal blood, cord blood and placenta tissue. RESULTS: The mean total mercury concentration in maternal blood, cord blood and placenta tissue was 9.1 +/- 0.40 microgram/l, 10.0 +/- 0.55 microgram/l and 19.2 +/- 1.8 ng/g, respectively. Eighty-nine percent of the maternal blood mercury concentrations exceeded the US National Research Council recommended value of 5.8 microgram/l. Fish consumption while pregnant correlated significantly with maternal blood and cord blood mercury concentrations. CONCLUSIONS: Total mercury concentrations of maternal blood, cord blood and placenta tissue commonly exceeded recommended values, and were higher in women who ate fish more than three times a week while pregnant.

The use of gene silencing to study the role of dopa decarboxylase in mosquito melanization reactions.

Mosquito melanization involves hydroxylation of tyrosine to dopa, which then is oxidized to dopaquinone by phenoloxidase, or decarboxylated to dopamine by dopa decarboxlase (DDC). An Armigeres subalbatus cDNA encoding DDC was cloned and real-time PCR analysis revealed increased transcripts in blood-fed and microfilariae (mf)-inoculated mosquitoes. A double subgenomic Sindbis virus was used to silence DDC and assess its role in melanization of mf. DDC transcription and activity were significantly decreased in silenced mosquitoes, as was the degree of mf melanization 48 h postinoculation; however, melanization increased after 72 and 96 h, demonstrating that DDC influences the rate of melanization. DDC-silenced mosquitoes also exhibit high mortality, over-feeding and abnormal movement, consistent with an involvement of DDC in neurotransmission.

Incidence and severity of iris pigmentation on latanoprost-treated glaucoma eyes.

PURPOSE: The purpose of the present study was to investigate the incidence and severity of iridial pigmentation under latanoprost topical use on brown eyes in Taiwan. METHODS: Retrospective review study was conducted from April 1999 to October 2001 in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan, for glaucoma clinic monthly follow-up patients; 140 open-angle glaucoma patients on 0.005% latanoprost were enrolled. Analyses of iridial pigmentation incidence, grading, patient age distribution, side effect, and time course were performed. Boys-Smith pigment gradation lens was used as standard for semiquantitative iris pigmentation grading. RESULT: Before 0.005% latanoprost use, 90% of the patients enrolled were noted with iridial pigmentation grade I, and 10% were with grade I-II, but not reaching grade II scale standard. A total of 60 patients on 0.005% latanoprost developed increased pigmentation of the iris during the follow-up period. An increase of iris pigmentation was noted after an average of 7.27 months use of latanoprost (range 1-19 months, SD 2.65 months). For iridial pigmentation grading, 57.1, 30.7, 10.0, and 2.1% of our patients were noted to have grade I, II, III, and IV respectively. Most patients with latanoprost-induced iris hyperpigmentation were with grade II iridial pigmentation. There were 15 patients (10.7%) (10 female and five male) with hypertrichosis in the study group who were not compatible with the iridial pigmentation status. Among these patients, female patients had higher incidence of hypertrichosis than males, but this did not bother them. Only four patients (2.8%) were with conjunctiva chemosis and three patients (2.1%) with lid margin hyperpigmentation. CONCLUSION: Contrary to the belief that latanoprost rarely caused iris hyperpigmentation in yellow-brown eyes, our study showed that 42.8% iris hyperpigmentation did occur, especially after continual use for around 7 months. Higher hyperpigmentation incidence were noted in male than in female patients. This might be due to stronger adrenergic incidence in male than in female patients. Although hypertrichosis and increasing eyelid pigmentation together with iridial pigmentation represented a potentially permanent cosmetic side effect, they are very rare and occurred in no more than 3% in our patients. It is a good way to take Boys-Smith pigment gradation lens for iridial pigmentation grading and for long-term continual evaluation. The doctors should exert great care in differentiating drug-induced iris pigmentation and iris nevi from early stage uveal melanoma.

Coherent electron transport in a Si quantum dot dimer.

We show that the coherence of charge transfer through a weakly coupled double-dot dimer can be determined by analyzing the statistics of the conductance pattern, and does not require a large phase coherence length in the host material. We present an experimental study of the charge transport through a small Si nanostructure, which contains two quantum dots. The transport through the dimer is shown to be coherent. At the same time, one of the dots is strongly coupled to the leads, and the overall transport is dominated by inelastic cotunneling processes.

Sacral parasite conjoined twin.

BACKGROUND: A variant of conjoined twins is one in which one twin is incomplete. CASE: A female infant was born vaginally at 40 weeks' gestation to a healthy primipara. No important abnormalities were noted during prenatal examinations. The infant was fully developed in all external aspects except for a parasitic body conjoined with her sacrococcygeal region. Separated by operation 2 weeks after birth, the parasite contained lower limbs, adipose tissue, muscles, and a bowel sac. Over 4 years of observation, no abnormalities have been found since the operation. CONCLUSION: Obstetricians should be aware of the existence of a parasite twin during prenatal examinations and of the importance of the differential diagnosis of parasite and teratoma, a neoplasm with malignant potential.

Magnetically induced reconstruction of the ground state in a few-electron Si quantum dot.

We report unexpected fluctuations in the positions of Coulomb blockade peaks at high magnetic fields in a small Si quantum dot. The fluctuations have a distinctive sawtooth pattern: as a function of magnetic field, linear shifts of peak positions are compensated by abrupt jumps in the opposite direction. The linear shifts have large slopes, suggesting formation of the ground state with a nonzero angular momentum. The value of the momentum is found to be well defined, despite the absence of the rotational symmetry in the dot.

Regional expression of inducible nitric oxide synthase in the kidney in dogs with unilateral ureteral obstruction.

PURPOSE: In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medullary tissue hypoxia. We examined the expression of inducible nitric oxide synthase, a product of a hypoxia sensitive gene, in the cortex and medulla in dogs with unilateral ureteral obstruction for 21 hours. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral obstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. RESULTS: Ureteral obstruction raised mean ureteral pressure plus or minus standard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obstruction mean renal blood flow was 116 +/- 10 ml. per minute, lower than the 213 +/- 22 ml. per minute in sham operated dogs (p <0.01). After unilateral ureteral obstruction release the mean glomerular filtration rate was 9.5 +/- 2.1 ml. per minute, lower than the 27.3 +/- 1.8 ml. per minute in the contralateral unobstructed kidney (p <0.01). Western blot analysis showed that mean nitric oxide synthase/beta-actin in the cortex of the obstructed kidney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densitometry units in the unobstructed contralateral kidney (p <0.05). In contrast, mean nitric oxide synthase/beta-actin in the medulla of the obstructed kidney was 1.29 +/- 0.33 densitometry units, greater than the 0.34 +/- 0.03 densitometry units in the unobstructed kidney (p <0.05). Immunohistochemistry revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. CONCLUSIONS: Unilateral ureteral obstruction enhances nitric oxide synthase expression in the medulla but not in the cortex. This increased expression in the medulla may be the result of increased medullary hypoxia in unilateral ureteral obstruction, possibly contributing to medullary hyperemia after unilateral ureteral obstruction release.

Hospital ownership and cost and quality of care: is there a dime's worth of difference?

Nonprofit organizations may predominate when output quality is difficult to monitor. Hospital care has this characteristic. This study compared program cost and quality of care for Medicare patients hospitalized following onset of four common conditions by hospital ownership. Payments on behalf of Medicare patients admitted to for-profit hospitals during the first 6 months following a health shock were higher than for those admitted to other hospitals. With quality measured in terms of survival, changes in functional and cognitive status, and living arrangements, we found no differences in outcomes by hospital ownership.

17Beta-estradiol inhibits oxidized low density lipoprotein-induced generation of reactive oxygen species in endothelial cells.

Increase of intracellular reactive oxygen species (ROS) has been proposed to cause endothelial injury, and oxidized LDL (oxLDL) actions are associated with an early increase of ROS. Estrogen protects vascular cells partly via its antioxidant effects and by preventing lipid peroxidation. However, whether it can inhibit oxLDL-induced stimulation of ROS generation in endothelial cells is unknown. We utilized the fluorescent dye (DCFH-DA) to measure ROS generation and compared the stimulant effect of tert-butylhydroperoxide (TBH) and oxLDL in human umbilical vein endothelial cells (HUVECs). We found that TBH, H2O2, and oxLDL rapidly stimulated ROS generation, and in a dose-dependent manner with TBH. A concentration of estrogen effective in preventing lipid peroxidation was employed either by pretreatment of cells 18 h prior to or by direct co-incubation (30 min) with HUVEC and oxLDL. Estrogen (54 microM) pretreatment significantly suppressed both TBH- and oxLDL- induced stimulation of ROS generation. Both 1 and 54 microM concentration of estrogen could directly inhibit oxLDL-induced ROS production in HUVECs. Thus, either 18 h pretreatment or 30 min co-incubation with estrogen reduced stimulated ROS generation, suggesting that both cellular and direct actions of estrogen may be involved.

Contaminated site remedial investigation and feasibility removal of chlorinated volatile organic compounds from groundwater by activated carbon fiber adsorption.

Groundwater contaminated by dense, non-aqueous phase liquids (DNAPLs) such as chlorinated solvents has become a serious problem in some regions of Taiwan. The sources of these contaminants are due to industrial discharges. These chlorinated volatile organic compounds (VOCs) have been proven to be carcinogenic to humans. The groundwater is used for domestic drinking water supply in some cities of Taiwan and the severely contaminated groundwater has to be treated in order to meet the requirement of drinking water standards. This study covers two areas of work. In the first part, polluted groundwater samples were collected from the contaminated site and analytical results indicated measurable concentrations of 12 representative chlorinated VOCs in water samples. The primary VOCs detected included trichloroethene (TCE), tetrachloroethene (PCE), 1,1,2-trichloroethane (1,1,2-TCA), and 1,1-dichloroethene (1,1-DCE). Second, to remove VOCs groundwater was treated using adsorption on activated carbon fiber (ACF). This involved pumping groundwater through vessels containing ACF. Most VOCs, including TCE, PCE, 1,1,2-TCA, and DCE, were readily adsorbed onto ACF and are removed from the water stream. Our study showed that the technology was able to significantly reduce chlorinated VOCs concentrations in groundwater.

Neuro-ophthalmic complications of raised intracranial pressure, hydrocephalus, and shunt malfunction.

1. Ophthalmic signs are important for the diagnosis and management of elevated intracranial pressure. 2. Visual loss, visual field loss, dorsal midbrain syndrome, and acute papilledema may occur well in advance of ventricular dilation. 3. For younger patients with hydrocephalus, amblyopia should be checked for, and the absence of papilledema does not ensure normal intracranial pressure. 4. Treatment should be delivered to control intracranial pressure and preserve vision in a timely fashion.

The price elasticity of opium in Taiwan, 1914-1942.

Between 1895 and 1945, the Japanese colonial government virtually eliminated opium use in Taiwan by licensing and treating existing users, prohibiting sales to others, and raising the price. We evaluate these policies using a two-part model to describe the fraction of the population using opium and consumption among users, and the rational addiction model by Becker et al. (1991). We confirm that opium is addictive and find no evidence supporting the rational addiction hypothesis. Demand is price-elastic with estimated short- and long-run demand elasticities of -0.48 and -1.38. These results have implications for control of other addictive substances.

Renal actions of endothelin-1 under endothelin receptor blockade by BE-18257B.

PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium, causes profound renal vasoconstriction by binding to ET-A receptors. The present study examined the renal actions of ET-1 after ET-A receptors were blocked by BE-18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal hemodynamics and clearance measurements were obtained in anesthetized dogs after intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET-1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function. In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and 40%, respectively) without altering arterial pressure. Urinary volume and sodium excretion were not changed but osmolality decreased significantly. In Group 3, BE-18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and increased GFR by 40% without altering arterial pressure, associated with significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET-1 induced decrease in RBF and raises GFR, and leads to a diuresis and natriuresis.

Activation of endothelium-derived relaxing factor system in acute unilateral ureteral obstruction.

PURPOSE: To investigate the effects of 1-arginine, a substrate for nitric oxide (NO) synthase, on renal hemodynamics in acute ureteral obstruction (UUO). MATERIALS AND METHODS: Renal blood flow (RBF) and ureteral pressure (UP) were measured in anesthetized dogs with or without UUO. RESULTS: In 9 dogs (Group 1), RBF was 212 +/- 13 ml./min. before UUO, and significantly increased to 302 +/- 18 and 268 +/- 9 ml./min. at 90 and 140 min. post-UUO, respectively, associated with a marked increase in UP from 3 +/_ 1 mm. Hg to 73 +/- 5 and 83 +/-2 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs (Group 2) prostaglandin synthesis was inhibited with meclofenamate (5 mg./kg., i.v.). After UUO, RBF did not change significantly and the increase in UP was markedly attenuated when compared with Group 1, as UP rose only to 27 +/-3 and 34 +/- 4 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs pre-treated with meclofenamate, L-arginine was infused into the renal artery at 5 mg./kg./min. at 90 min. after UUO (Group 3). Prostaglandin synthesis inhibition prevented renal vasodilation after UUO and significantly attenuated the increase in UP. Upon infusion of L-arginine, RBF and UP rose sharply from 202 +/- 16 ml./min. and 24 +/- 6 mm. Hg to 264 +/- 22 ml./min. and 70 +/- 4 mm. Hg, respectively, at 140 min. post-UUO (p <0.001), values approaching those in Group 1. In sham-operated dogs, L-arginine infusion did not alter RBF in dogs with or without pretreatment with meclofenamate. CONCLUSION: In UUO the L-arginine-NO pathway is activated, contributing to renal vasodilation and a marked increase in UP.

Contribution of endothelin-1 to renal vasoconstriction in unilateral ureteral obstruction: reversal by verapamil.

PURPOSE: In unilateral ureteral obstruction (UUO) vasoconstriction occurs both during and after release of UUO. ET-1, an endogenous peptide, causes marked vasoconstriction mediated by an increase in cytosolic calcium. We measured renal output of endothelin-1 (ET-1) in dogs with UUO and examined if the renal vasoconstriction that persisted after release of UUO could be reversed by a calcium antagonist, verapamil. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed in anesthetized mongrel dogs in three groups. Group I consisted of 9 dogs with sham-operation. Group 2 consisted of 7 dogs in whom ureteral obstruction was released 1.9 hours after UUO. Group 3 consisted of 5 dogs in whom verapamil was infused into the renal artery at two doses (5 and 10 microg./min., respectively) after release of UUO of 19-hour duration. ET-1 concentrations (measured by radioimmunoassay) were determined for renal venous and arterial plasma. RESULTS: In Group 1 renal venous plasma ET-1 level was 16.7 +/- 2.2, significantly lowered than 22.8 +/- 3.2 pg./ml. in arterial plasma, indicating a net clearance of ET-1. In Group 2 and 3, renal venous plasma ET-1 levels (28.2 +/- 5.2 and 27.2 +/- 2.4 pg./ml., respectively) were significantly greater than those in arterial plasma (24.2 +/- 5.7 and 17.4 +/- 0.8 pg./ml., respectively), indicating a net output of ET-1 in the kidney, In addition, renal vasoconstriction occurred in Groups 2 and 3 as indicated by significantly lower renal blood flow and GFR than those in Group 1. In Group 3, intrarenal infusion of verapamil at two doses did not change arterial pressure but caused an ipsilateral, significant increase in RBF (from 132 +/- 4 17 to 1.84 +/- 19 and 180 +/- 16 ml./min., respectively) and dose-dependent increases in GFR (from 12 +/- 2 to 25 +/- 3 and 38 +/- 7 ml./min., respectively), associated with a profound dose-dependent ipsilateral diuresis and natriuresis. CONCLUSION: Profound renal vasoconstriction in UUO was associated with an increase in renal production of ET-1, possibly contributing to renal vasoconstriction, and was reversed by intrarenal infusion of verapamil.

Molecular cloning and analysis of a HSP (heat shock protein)-like 42 kDa antigen gene of Mycoplasma hyopneumoniae.

The recombinant clone expressing the 42 kDa protein (P42) of Mycoplasma hyopneumoniae in Escherichia coli was analyzed. The 4.4 kb HindIII-Xmal DNA fragment expressing the p42 gene product encodes three ORFs: p42 and p16 in the forwarding strand, p24 in the reverse strand. Sequence comparisons revealed that p42 could be part of a p65 gene, and has 62% identities with Mycoplasma genitalium HSP70 gene and 56% identities with Bacillus subtilis dnaK gene; p16 and p24 genes share 73% and 47% identities with Erysipelothrix rhusiopathiae dnaJ gene and Pseudomonas fluorescens uvrC gene, respectively. Further analysis demonstrated that P42 is indeed a heat shock protein and the monospecific antibodies against P42 can block the growth of Mycoplasma hyopneumoniae.

Reversal of trimethoprim-induced antikaliuresis.

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) causes hyperkalemia, thought to result from TMP-induced blockade of amiloride-sensitive Na(+)-channels in the distal nephron. The present study was performed in anesthetized dogs to determine if increasing distal sodium delivery affects this antikaliuretic effect. In Group 1, intrarenal infusion of vehicle did not alter renal function. In Group 2, i.v. infusion of amiloride led to diuresis, natriuresis and antikaliuresis associated with a reduction of the transtubular potassium gradient (TTKG) in both kidneys. Intrarenal infusion of TMP (0.2 mg/kg/min) into the left kidney did not further alter these parameters. In groups 3 and 4, intrarenal infusion of TMP caused an ipsilateral diuresis, natriuresis, antikaliuresis and a reduction in (TTKG) without affecting the contralateral kidney. The TMP infusion was followed by furosemide (20 mg i.v.) in group 3 and acute saline loading in group 4. Despite continuous TMP infusion, both furosemide and saline loading reversed the antikaliuretic effect of TMP in the ipsilateral kidney and was associated with a similar kaliuresis, diuresis, natriuresis and decrease in urine osmolality in both kidneys. The TTKG following furosemide or saline loading increased in the ipsilateral kidney and decreased in the contralateral kidney. In all groups the systemic and renal hemodynamics remained unchanged. These results suggest that acute administration of TMP inhibits the amiloride-sensitive Na(+)-channel and K+ secretion in the distal nephron. Maneuvers that increase distal Na+ delivery can abrogate TMP's antikaliuretic effect due, in part, to an increase of the low TTKG observed with TMP.