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Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed. Early diagnosis and immediate initiation of treatment are essential for effective TBM control. A systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against Mycobacterium tuberculosis in the cerebrospinal fluid (CSF), according to standard methods. Test performance was summarized using a bivariate random-effects meta-analysis., Methods: Studies were identified by a search of the literature, up to July 25, 2015, in the EMBASE and MEDLINE databases via Ovid SP and PubMed. The Cochrane Library was also searched for original, peer-reviewed molecular epidemiology studies that reported the diagnosis of TBM based on antibody detection in the CSF., Results: Thirty-six articles (58 studies) were identified. The sensitivity of antibody detection was 0.75 (95% confidence interval (CI) 0.66-0.82), specificity was 0.98 (95% CI 0.96-0.99), and the area under the receiver operating characteristic curve (AUROC) was 0.97 (95% CI 0.95-0.98). By subgroup analysis, the detection of anti-M37Ra was the highest (AUROC 0.99, 95% CI 0.98-1.00), followed by anti-antigen 5 (AUROC 0.99, 95% CI 0.97-0.99) and anti-M37Rv (AUROC 0.97, 95% CI 0.95-0.98)., Conclusions: For the early diagnosis of TBM based on antibodies in the CSF, the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The underthrusting of continental crust during mountain building is an issue of debate for orogens at convergent continental margins. We report three-dimensional seismic anisotropic tomography of Taiwan that shows a nearly 90° rotation of anisotropic fabrics across a 10- to 20-kilometer depth, consistent with the presence of two layers of deformation. The upper crust is dominated by collision-related compressional deformation, whereas the lower crust of Taiwan, mostly the crust of the subducted Eurasian plate, is dominated by convergence-parallel shear deformation. We interpret this lower crustal shearing as driven by the continuous sinking of the Eurasian mantle lithosphere when the surface of the subducted plate is coupled with the orogen. The two-layer deformation clearly defines the role of subduction in the formation of the Taiwan mountain belt., (Copyright © 2015, American Association for the Advancement of Science.)

In Taiwan, autism spectrum disorders (ASDs) are an emerging public health concern. The ongoing scientific progress for understanding the genetic etiology of ASD makes it increasingly important to examine how parents of children with ASD perceive the causes and recurrence risk of having another child with ASD. These perceptions may influence their family planning, attitudes toward genetic services, and willingness to take their children for ASD genetic testing. However, previous studies addressing this issue were conducted primarily in Western countries. As culture might shape an individual's views of genetic/genomic disorders, this first-of-its-kind study examined the perceptions of the genetic etiology for ASD and the recurrence risk among Taiwanese parents of children affected with ASD. In-depth, semi-structured interviews were conducted among 39 parents having at least one child with ASD. Although the majority of participants believed that ASD has a genetic link, less than half perceived genetic factors as the cause of their own child's ASD. Moreover, most participants articulated their recurrence risk incorrectly. Some parents were concerned about their doctors' limited genomic competencies. To provide parents with better education, counseling, and support for making reproductive decisions, ASD-related genomic education among Taiwanese physicians is needed., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Current T2-weighted imaging takes >3 minutes to perform, for which the ultrafast transition into driven equilibrium (TIDE) technique may be potentially helpful. This study qualitatively and quantitatively evaluates the imaging of transition into driven equilibrium of the balanced steady-state free precession (TIDE) compared with TSE and turbo gradient spin-echo on T2-weighted MR images., Materials and Methods: Thirty healthy volunteers were examined with T2-weighted images by using TIDE, TSE, and turbo gradient spin-echo sequences. Imaging was evaluated qualitatively by 2 independent observers on the basis of a 4-point rating scale regarding contrast characteristics and artifacts behavior. Image SNR and contrast-to-noise ratio were quantitatively assessed., Results: TIDE provided T2-weighted contrast similar to that in TSE and turbo gradient spin-echo with only one-eighth of the scan time. TIDE showed gray-white matter differentiation and iron-load sensitivity inferior that of TSE and turbo gradient spin-echo, but with improved motion artifacts reduction on qualitative scores. Nonmotion ghosting artifacts were uniquely found in TIDE images. The overall SNRs of TSE were 1.9-2.0 times those of turbo gradient spin-echo and 1.7-2.2 times of those of TIDE for brain tissue (P < .0001). TIDE had a higher contrast-to-noise ratio than TSE (P = .169) and turbo gradient spin-echo (P < .0001) regarding non-iron-containing gray matter versus white matter. TIDE had a lower contrast-to-noise ratio than turbo gradient spin-echo and TSE (P < .0001) between iron-containing gray matter and white matter., Conclusions: TIDE provides T2-weighted images with reduced scan times and reduced motion artifacts compared with TSE and turbo gradient spin-echo with the trade-off of reduced SNR and poorer gray-white matter differentiation., (© 2014 by American Journal of Neuroradiology.)

Cucurbitacin E (CuE) or α-elaterin is a natural compound previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study investigated the anticancer effects of CuE on colorectal cancer (CRC) using primary cell lines isolated from five CRC patients in Taiwan, Specifically, we explored the anti-proliferation and cell cycle G2/M arrest induced by CuE in CRC cells. MPM-2 flow cytometry tests show that CuE-treated cells accumulated in metaphase (CuE 2.5-7.5 μM). Results further indicate that CuE produced G2/M arrest as well as the downregulation of CDC2 and cyclin B1 expression and dissociation. Both effects increased proportionally with the dose of CuE; however, the inhibition of proliferation, arrest of mitosis, production of reactive oxygen species (ROS), and loss of mitochondrial membrane potential (ΔΨm) were found to be dependent on the quantity of CuE used to treat the cancer cells. In addition, cell cycle arrest in treated cells coincided with the activation of the gene GADD45(α, β, γ). Incubation with CuE resulted in the binding of GADD45γ to CDC2, which suggests that the delay in CuE-induced mitosis is regulated by the overexpression of GADD45γ. Our findings suggest that, in addition to the known effects on cancer prevention, CuE may have antitumor activities in established CRC.

Cucurbitacin E (CuE) is a natural compound previously shown to have anti-feedant, antioxidant and antitumor activities as well as a potent chemo-preventive action against cancer. The present study investigates its anti-proliferative property using MTT assay; CuE demonstrated cytotoxic activity against malignant glioma GBM 8401 cells and induced cell cycle G2/M arrest in these cells. CuE-treated cells accumulated in metaphase (CuE 2.5-10 μM) as determined using MPM-2 by flow cytometry. We attempted to characterize the molecular pathways responsible for cytotoxic effects of CuE in GBM 8401 cells. We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. The CuE reduced the expression of 558 genes and elevated the levels of 1354 genes, suggesting an existence of the common pathways involved in induction of G2/M arrest. We identified the RB (GADD45β and GADD45γ) and the p53 (GADD45α) signaling pathways as the common pathways, serving as key molecules that regulate cell cycle. Results indicate that CuE produced G2/M arrest as well as the upregulation of GADD45 γ and binding with CDC2. Both effects increased proportionally with the dose of CuE, suggesting that the CuE-induced mitosis delay is regulated by GADD45γ overexpression. Our findings suggest that, in addition to the known effects on cancer prevention, CuE may have antitumor activity in glioma therapy.

Purpose: This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation., Materials and Methods: Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections., Results: Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (P<0.05). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived on T2WI, DWI or CE-T1WI than ADC (P<0.05). At the last imaging time point, a significant increase in Evans Blue extravasation and a significant decrease in Nissl-positive cells numbers were noted in the vehicle-treated MCAO injured animals. The lesion volumes derived from T2WI, DWI, CE-T1WI, and Evans blue extravasation as well as the reduced numbers of Nissl-positive cells were all significantly attenuated in the agmatine-treated rats compared with the control ischemia rats (P<0.05)., Conclusion: Our results suggest that agmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Macrophages are major immune cells and play an important role in modulating homeostasis and the immune defense mechanism. In inflammatory responses to the infection of pathogens, macrophages are activated, producing various inflammatory mediators. Snake venom C-type lectin proteins (snaclecs) have diverse targets, including platelet GPVI, GPIb, integrin α2β1 or CLEC-2 expressed in platelets, endothelial cells or myeloid cells., Methods: In this study, murine macrophages (RAW 264.7 cells) and human monocytes (THP-1) were treated with different snaclecs, including aggretin, gramicetin, trowaglerix and convulxin, in the absence or presence of LPS for 24 h., Results: The production of cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in supernatants was measured by ELISA. Aggretin increased the production of TNF-α and IL-6 in both RAW264.7 and THP-1 cells; however, the other snaclecs did not. Aggretin induced extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) tyrosine phosphorylation of RAW264.7 cells. Pretreatments with inhibitor of ERK, JNK, p38 or NF-κB abolished cytokine release caused by aggretin. Aggretin bound to THP-1 cells in a concentration-dependent manner and it displaced the CLEC-2 mAb binding to THP-1 cells and the immobilized aggretin selectively bound to CLEC-2 of both platelets and THP-1 cell lysates. Furthermore, aggretin elevated the plasma level of IL-6 in ICR mice as it was administered intramuscularly., Conclusion: These results indicate that aggretin may induce cytokine TNF-α/IL-6 release via interacting with CLEC-2 receptor and the subsequent MAPK and NF-κB activation in monocytes/macrophages., (© 2010 International Society on Thrombosis and Haemostasis.)

In the dipteran Drosophila, the genes bicoid and hunchback work synergistically to pattern the anterior blastoderm during embryogenesis. bicoid, however, appears to be an innovation of the higher Diptera. Hence, in some non-dipteran insects, anterior specification instead relies on a synergistic interaction between maternally transcribed hunchback and orthodenticle. Here we describe how orthologues of hunchback and orthodenticle are expressed during oogenesis and embryogenesis in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum. A. pisum hunchback (Aphb) mRNA is localized to the anterior pole in developing oocytes and early embryos prior to blastoderm formation - a pattern strongly reminiscent of bicoid localization in Drosophila. A. pisum orthodenticle (Apotd), on the other hand, is not expressed prior to gastrulation, suggesting that it is the asymmetric localization of Aphb, rather than synergy between Aphb and Apotd, that regulates anterior specification in asexual pea aphids.

Aims: To devise an ex vivo model to test the efficacy of irrigation (static/dynamic) in removing a bio-molecular film from root canal walls., Methodology: Forty human teeth with single straight canals were randomly allocated to two groups for static (n = 20) or dynamic (n = 20) irrigation. The root canals were prepared to different apical sizes (20, 40) and tapers (0.04, 0.08). The teeth were split longitudinally into two, stained collagen was applied to the canal surfaces and the tooth reassembled in a silicone matrix for dynamic or static irrigation. Digital images of the canal surface were taken before and after irrigation with 9, 18, 27 and 36 mL solution. The percentage of canal surface covered with stained collagen was quantified (ipWin4). The data were analysed using paired t-tests and linear regression models., Results: All the five explanatory variables: 'volume of irrigant used', 'mode of irrigation', 'orientation of open port of needle', 'corono-apical level of canal' and 'root canal dimension' had a significant (P < 0.001) influence on outcome of irrigation. The corono-apical level of canal was the most dominating factor. After irrigation, the apical third had 19.9% and 33.8% less area covered with the bio-molecular film than the middle and coronal thirds respectively., Conclusions: The stained collagen bio-molecular film could not be removed completely by either static or dynamic irrigation. Factors influencing removal, in rank order of decreasing priority, were: corono-apical level, apical size and taper of canal preparation, and dynamic/static irrigation.

The aim was to study the effects of listening to music on gastric myoelectrical activity in healthy humans. Gastric myoelectrical activity was recorded using surface electrogastrography from 17 healthy volunteers before and for 30 min after they listened to music. All subjects listened to the same music. Ten perceived the music as enjoyable and seven did not. The percentages of normal slow wave, dominant frequency and dominant power did not differ significantly between baseline and during music intervention. An analysis of covariance model that included the subjects' feelings about the music and dominant power showed significantly higher dominant power during music intervention in subjects who enjoyed the music (p < 0.01). In the individuals who enjoyed the music, dominant power (55.0 +/- 9.2 dB) was significantly higher during music intervention than at baseline (49.5 +/- 6.8 dB, p = 0.03). In the subjects who did not enjoy the music, dominant power was significantly lower during music intervention than at baseline (48.8 +/- 6.8 and 55.7 +/- 6.2 dB, respectively; p < 0.01). Listening to enjoyable music increases the amplitude of gastric myoelectrical activity in healthy humans. Music therapy may improve gastric motility and may be used to stimulate gastric emptying.

Background and Purpose: The relationship between the local blood oxygen level-dependent (BOLD) signals caused by neural stimulation (fBOLD) and the global BOLD signals induced by hypercapnia (hBOLD) has not been fully investigated. In this study, we examine whether fBOLD is modulated by hBOLD signals, by means of experiments using a relatively wide range of inhaled carbon dioxide (CO(2)) for a long duration of 5 minutes., Materials and Methods: Ten healthy volunteers were recruited, each undergoing 6 separate experiments by inhaling gas mixtures with different fractions of CO(2) (room air, 3%-7%). Each experiment contained 3 phases, prehypercapnic, hypercapnic, and posthypercapnic, during which boxcar visual stimulus was given. The local fBOLD signals were measured from areas showing activation patterns highly correlated with the visual stimulus paradigm, whereas the global hBOLD signals were measured from areas showing no visual activations. Percentage changes in fBOLD during transient-state hypercapnia and steady-state hypercapnia were both investigated in response to varying degrees of hypercapnic perturbations., Results: The hBOLD signals increased with increase of inhaled CO(2) fractions. The duration for the hBOLD signals to reach steady state prolonged with increase of inhaled CO(2) fractions. Normalized fBOLD ratio was inversely related to the inhaled CO(2) during steady-state hypercapnia but showed positive association with hBOLD during transient-state hypercapnia., Conclusion: Our study concludes that the steady-state fBOLD signal intensity is dependent on and inversely related to the hBOLD signals. Previous reports documenting independent and additive relationships between hBOLD and fBOLD may likely be due to transient-state observations.

Background: Warfarin is a mainstay of therapy for conditions associated with an increased risk of thromboembolic events. However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response., Objective: We tested for association between single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly warfarin dose required to maintain patients at their desired anticoagulation target., Methods: The sample consisted of 93 European-American patients from anticoagulation clinics at the University of North Carolina at Chapel Hill. Data on mean weekly warfarin dose were collected over a mean treatment period of 20.6 months. ANCOVA models were used and haplotype analysis was performed., Results: Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p<0.0001). The mean weekly dose by genotype ranged from approximately 27 to 47 mg. There was no evidence for an association between either of the two CYP2C9 polymorphisms studied, CYP2C9*2 and CYP2C9*3. CYP2C9*3 was significantly (p = 0.05) associated with average warfarin dosage after adjustment for VKORC1*1173., Conclusions: These results are of considerable clinical interest and confirm recently published results regarding the role of these two genes in modifying warfarin metabolism and maintenance dosage. The consistent findings regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance dosage represent a clinically useful proof of principal for the use of pharmacogenomic information in medicine and may lead to improved understanding of warfarin's actions.

Glial cells in both central and peripheral nervous systems are connected by gap junctions, which allow electrical and metabolic coupling between them. In spite of the great current interest in aging of the nervous system, the effect of aging on glial cell coupling received little attention. We examined coupling between satellite glial cells in murine dorsal root ganglia using the dye coupling technique and electron microscopy. We studied mice at ages of postnatal 90-730 days. Dye coupling incidence between satellite glial cells associated with a single neuron increased from 24.2% at postnatal day 90 to 50.5% at postnatal day 730. Dye coupling between satellite glial cells that are in contact with two or more neurons increased from 2.7% at postnatal day 90 to 18.6% at postnatal day 730 (P<0.05). Examination of the ganglia with the electron microscope showed that the number of gap junctions per 100 microm2 of surface area of satellite glial cells increased from 0.22 at postnatal day 90 to 1.56 at postnatal day 730 (P<0.01). The mean length of individual gap junctions did not change with age. These results provide strong evidence for an increase of functional coupling between satellite glial cells during life. This increase is apparently due to an increase in the total area of the system of gap junctions connecting these cells.

Background: Hyperbaric oxygen (HBO) attenuates lipopolysaccharide (LPS)-induced acute lung injury. This beneficial effect of HBO involves inhibition of inducible nitric oxide synthase (iNOS) expression and subsequent nitric oxide (NO) biosynthesis. We sought to investigate the role of heme oxygenase-1 (HO-1) on this HBO inhibition of iNOS induction and acute lung injury in septic rat lungs., Methods: Before the experiment, 72 rats were randomly allocated to receive HBO or air treatment. With or without HBO pre-treatment, the rats were further divided into the following subgroups (n = 6): (i) LPS injection, (ii) normal saline (N/S) injection, (iii) hemin (a HO-1 inducer) plus LPS, (iv) hemin alone, (v) tin protoporphyrin (SnPP; a HO-1 inhibitor) plus LPS, and (vi) SnPP alone. All rats were maintained for 6 h and then sacrificed with a high-dose pentobarbital injection. Lung injuries and relevant enzymes expression were thus assayed., Results: Histological analysis, PMNs/alveoli ratio, and wet/dry weight ratio measurements demonstrated that LPS caused significant lung injury and HBO and/or hemin significantly attenuated this LPS-induced lung injury. Increased pulmonary iNOS expression and NO production were associated with lung injury. Induction of HO-1, by HBO and/or hemin, significantly attenuated this LPS-induced iNOS expression and acute lung injury. SnPP, on the contrary, offset the effects of HBO and worsened the LPS-induced lung injury., Conclusions: HBO may act through inhibiting pulmonary iNOS expression to attenuate LPS-induced acute lung injury in septic rats. Furthermore, this HBO attenuation of iNOS expression involves HO-1 induction.

Preventing accidents caused by drowsiness behind the steering wheel is highly desirable but requires techniques for continuously estimating driver's abilities of perception, recognition and vehicle control abilities. This paper proposes methods for drowsiness estimation that combine the electroencephalogram (EEG) log subband power spectrum, correlation analysis, principal component analysis, and linear regression models to indirectly estimate driver's drowsiness level in a virtual-reality-based driving simulator. Results show that it is feasible to quantitatively monitor driver's alertness with concurrent changes in driving performance in a realistic driving simulator.

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] <90/140 mmHg) and responded to treatment (reduction from baseline in trough seated DBP > or = 10 mmHg and/or post-treatment DBP <90 mmHg; reduction from baseline in trough seated SBP > or = 10 mmHg and/or post-treatment SBP <140 mmHg) with telmisartan 40 mg compared with enalapril 10 mg. Although both treatments were well tolerated, the incidence of cough was markedly lower with telmisartan 40 mg (8.5%) than with enalapril 10 mg (18.4%) in this population of Taiwanese hypertensive patients.

Numerous studies have been done on the effect of nerve injury on neurons of sensory ganglia but little is known about the contribution of satellite glial cells (SCs) in these ganglia to post-injury events. We investigated cell-to-cell coupling and ultrastructure of SCs in mouse dorsal root ganglia after nerve injury (axotomy). Under control conditions SCs were mutually coupled, but mainly to other SCs around a given neuron. After axotomy SCs became extensively coupled to SCs that enveloped other neurons, apparently by gap junctions. Serial section electron microscopy showed that after axotomy SC sheaths enveloping neighboring neurons formed connections with each other. Such connections were absent in control ganglia. The number of gap junctions between SCs increased 6.5-fold after axotomy. We propose that axotomy induces growth of perineuronal SC sheaths, leading to contacts between SCs enveloping adjacent neurons and to formation of new gap junctions between SCs. These changes may be an important mode of glial plasticity and can contribute to neuropathic pain.

To evaluate the incidence and influencing factors related to preoperative and postoperative seizures, a retrospective analysis was performed in 190 patients with astrocytic tumours. Preoperative seizures occurred in 50 (26%) patients and 27 (54%) of the m had recurrent seizures. Late-onset seizures developed after craniotomy in 11 (8%) of 140 patients. Seizures at presentation were significantly correlated with age at diagnosis (P=0.0204) and pathological grade of tumour (P=0.0040). The patients aged less than 40 years had a high risk of seizures at presentation (odds ratio=3.076, P=0.0134). Postoperative seizures were significantly associated with the presence of preoperative seizures (P<0.0001), type or duration of preoperative seizures (P<0.0001, P<0.0001, respectively) and serum level of anticonvulsant drug (P=0.0068). However, only the presence of preoperative seizures had a potential for prediction of postoperative seizures when evaluated by logistic regression model (odds ratio=20.859, P=0.0001). Fifty-nine percent of patients with recurrent seizures and 64% of patients with late-onset seizures had seizures which occurred within 6 months after craniotomy. Despite therapeutic anticonvulsant levels, most postoperative seizures were associated with tumour recurrence or haemorrhage. Postoperative seizures commonly occurred relatively soon after craniotomy and prophylactic anticonvulsants should be given. In patients with postoperative seizures, particularly in the presence of therapeutic anticonvulsant level, brain computed tomography should be performed to exclude tumour recurrence or haemorrhage., (Copyright 2001 Harcourt Publishers Ltd.)

To investigate the effect of honey and sugars on the metabolism and disposition of naringin, rabbits were administered naringin alone and naringin with honey or its component sugars - fructose, glucose and sucrose in crossover designs. An HPLC method was developed to determine naringenin in serum after enzymatic hydrolysis. Our results indicate that honey, fructose and sucrose significantly reduced AUC(0-t) of naringenin by 41 %, 61 % and 45 %, respectively. In vitro studies using a rabbit feces suspension to incubate naringin without or with honey or the respective sugars were employed to investigate the mechanism of this interaction. The results indicated that honey and its component sugars did not affect the rate and extent of naringin hydrolysis, whereas the degradation of naringenin was significantly enhanced in the presence of honey and fructose. It could be concluded that concomitant intake of honey, fructose and sucrose resulted in the reduction of naringin absorption which could be attributable in part to the enhanced preabsorption degradation of absorbable naringenin in the large intestine.

Background: Although various endothelium-dependent relaxing factors (endothelial autacoids) are released upon the elevation of endothelial cytosolic free Ca2+ concentration (EC [Ca2+]i), the quantitative relationship between EC [Ca2+]i and vascular tone remains to be established. Moreover, whether the basal release of endothelial autacoids is modulated by basal EC [Ca2+]i is still unclear. We assessed these issues by using a novel method that allows simultaneous recording of EC [Ca2+]i and vascular displacement in dissected rat aortic segments., Results: Receptor-dependent (acetylcholine) or independent (ionomycin) agonists caused immediate EC [Ca2+]i elevation followed by vasorelaxation in preparations pre-contracted with phenylephrine. Low doses of agonists induced small EC [Ca2+]i elevations (about 100 nmol/L) and concomitant half-maximal vasorelaxation. At high doses, agonists elevated EC [Ca2+]i to micromol/L range with little additional vasodilatation. When EC [Ca2+]i was plotted against the vasorelaxation, the curves were almost identical for both acetylcholine and ionomycin treatments, in the presence or absence of various endothelial autacoid inhibitors. Calcium-free solution reduced basal EC [Ca2+]i and induced a drastic vasoconstriction. Endothelial autacoid inhibitors reduced EC [Ca2+]i changes and abolished both agonist-induced vasodilatation and calcium-free solution-induced vessel contraction. When the EC [Ca2+]i was completely chelated by 40 micromol/L BAPTA, the acetylcholine-evoked vasorelaxation could be abolished as well. However, when the EC [Ca2+]i was partially chelated by 20 micromol/L BAPTA, the acetylcholine-evoked vasorelaxation was almost unaffected., Conclusions: These results indicate that vascular tone is modulated by subtle changes of EC [Ca2+]i level, which seems to serve as an integrating signal in both basal and stimulated states.

Objective: To investigate the population constitution and geographical distribution of Plasmodium vivax in China using molecular technique., Methods: Blood-spot filter paper samples with related epidemiological data were collected from vivax malaria patients living in malarious area of 10 provinces (autonomous region) in China. Semi-nested- or nested-allelic-specific PCR genotyping method was used to identify CSP genotypes, families and types of Plasmodium vivax of each isolate from these patients., Results: Of 384 field isolates of Plasmodium vivax, 258 temperate zone family strains were identified, including 14 allelic variant genotypes spreading among 10 sampling provinces; allelic variants sized less than 731 bp were only seen in 5 provinces in southern China; 79 tropical zone family strains including 5 genotypes were also distributed in 5 provinces of southern China south to 25 degrees N. lat; and 14 PV Type-2 strains including 2 genotypes were found in some areas of Hainan and Yunnan Provinces. In addition, 33 isolates from genotype-mixed infections were revealed., Conclusion: At present, area north to 25 degrees N. lat. of the country is the sole area prevalent for Plasmodium vivax family strains of temperate zone; there is overlapping distribution of P. v. of temperate zone family and tropical zone family of this parasite in the southern China south to 25 degrees N. lat; where the most complex isolate constitution is in Yunnan and Hainan Provinces, and PV Type-2 strains have been found in some areas of the two provinces. Besides, there were 2 groups of genotype with distinct geographic distribution feature within the temperate zone family.

Chronic exercise enhances endothelium-dependent vasodilating responses. To investigate whether this is due to a change in endothelial Ca(2+) signaling, we examined intracellular Ca(2+) concentration ([Ca(2+)](i)) level in rat aortic endothelium in response to acetylcholine (ACh) or ATP. Four-week-old male Wistar rats were divided into control and exercise groups. The exercised animals ran on a treadmill at a moderate intensity for 60 min/day, 5 day/wk, for 10 wk. Rat aortas were then excised and loaded with fura 2. After the aortas were mounted on a flow chamber, these specimens were observed under an epifluorescence microscope equipped with ratio-imaging capability. Our results showed that 1) chronic exercise increased both ACh- and ATP-induced [Ca(2+)](i) responses; 2) ACh induced heterogeneous [Ca(2+)](i) elevation in individual endothelial cells; and 3) the exercise effect on ACh-evoked endothelial [Ca(2+)](i) elevation was inhibited by the Ca(2+) influx blocker SKF-96365, by a Ca(2+)-free buffer, or by high concentrations of extracellular K(+). We conclude that chronic exercise increases ACh-induced [Ca(2+)](i) elevation in rat aortic endothelium in situ, possibly by facilitating Ca(2+) influx.

The improved diagnostic capacity of computed tomography (CT) may have resulted in improved detection of intracranial tumors. We were interested to know whether the frequency of intracranial tumors has changed after the introduction of CT in Taiwan. The relative incidences of intracranial tumors in Taiwan were analyzed from the hospital based data. Our data showed that meningiomas were the most encountered intracranial tumors. Neuroepithelial tumors in our series (in the post-CT era) (23.9%) were apparently lower than those found in the pre-CT era (36.0%). However, the relative incidences of meningiomas and pituitary adenomas after the use of CT (24.2%, 21.1%, respectively) were much higher than those found before the use of CT (14.5%, 7.7%, respectively). Our data suggest that the increased incidence for benign tumors and the decreased incidence for malignant tumors may have resulted from the improved diagnostic capacity of CT, which reduces the number of undetected tumor cases.

The difference of prognosis in patients with the same WHO grade of astrocytic tumors suggests that such tumors comprise a heterogeneous group in biological behavior. The correlation between p53 immunoreactivity and prognosis has often been reported but remains controversial. From the perspective of clonal expansion of p53 immunopositive cells, the distribution patterns of p53 immunoreactivity can be divided into four types: negative, scattered, focally clustered, and diffusely clustered. The survival rate was evaluated by classifying the p53 immunoreactivity into two groups: the significantly immunopositive patterns (focally and diffusely clustered types) and the significantly immunonegative patterns (negative and scattered types). The survival analysis showed a highly significant difference between these two patterns within the same WHO grade of astrocytic tumors (p = 0.0185). Our studies demonstrate that the distribution patterns of p53 immunoreactivity, which reflect the trends of clonal expansion of p53 immunopositive cells, are significantly valuable in predicting the prognosis of patients with the same WHO grade of astrocytic tumors.

Background: Kawasaki disease (KD) is an acute febrile illness characterized by multiple clinical and biochemical features of inflammation and the most common complications of coronary artery abnormality (CAA). Haptoglobin (Hp) is an acute-phase protein whose phenotype is known to be involved in coronary artery diseases. In this paper, we report the investigation of the association of Hp phenotype with the formation of CAA in KD., Patients and Methods: Forty-seven consecutive patients with clinically diagnosed KD were admitted. Sera were taken before therapy of intravenous immunoglobulins (IVIG) plus aspirin, and levels of serum proteins were measured by a rate immunonephelometer. The echocardiographic criteria for coronary artery abnormality were evaluated during acute or subacute stages. Hp phenotyping was performed by Western immunoblotting., Results: Duration of fever at diagnosis of KD was significantly different between patients with Hp 2-2 (6.4 +/- 1.2 days, n = 25) and with Hp1 allele (Hp 2-1 plus Hp 1-1; 8.8 +/- 3.5 days, n = 22). In contrast, serum levels of Hp between KD patients with Hp2-2 and with Hp1 allele (297 +/- 121 mg dL-1 vs. 330 +/- 101 mg dL-1, respectively) was not significantly different. On the other hand, no patients with Hp 2-2 (0/25) were recognized as having KD in subacute stage. However, 5 out of 20 patients with Hp 2-1 were recognized in subacute stage, and their incidence of CAA was 80.0% (4/5)., Conclusions: Patients with Hp 2-1 have patterns of delayed or incomplete presentation of clinical symptoms. Therefore, the late diagnosis of KD is associated with haptoglobin phenotype.

Most existing knowledge about [Ca(2+)](i) signaling in vascular endothelium has been based on studies using endothelial cells cultured in vitro. To examine how endothelial cells behave in situ, we have developed a method to monitor single-cell [Ca(2+)](i) from Fura-2-loaded rat aortic segments. Fluorescence ratio images from large numbers of endothelial cells were acquired by using a flow chamber mounted on a dual-wavelength fluorescence microscope. Our results showed that either acetylcholine or histamine reversibly activated the vascular endothelium by eliciting M(3) or H(1) receptor-mediated [Ca(2+)](i) increases, respectively. The acetylcholine-evoked endothelial [Ca(2+)](i) elevation at the branch site (intercostal orifice) was much more pronounced than that at the non-branch area. However, endothelium at the branch site was relatively insensitive to histamine. Both acetylcholine-sensitive and histamine-sensitive endothelial cells were arranged in belts aligned along flow lines and were intercalated with each other. Data analyzed from 400 endothelial cells located at the non-branch site showed drastically heterogeneous [Ca(2+)](i) responses to a fixed concentration of either acetylcholine or histamine, differing by two orders of magnitude in individual cells. As a conclusion, vascular endothelial cells appear to have their own characteristic [Ca(2+)](i) 'fingerprint' to various agonists and they may function coordinately in situ.

Objective: To develop a new method of genotyping circumsporozoite protein (CSP) gene for identification of field isolates of Plasmodium vivax., Methods: Improved Chelex-100 ion-exchange method was used to extract DNA from blood filter paper samples, nested PCR and allele-specific PCR techniques, agarose gel electrophoresis analysis and dot/southern blotting-probe hybridization were employed for amplification, resolution and identification of the diagnostic fragments., Results: Using the nest-allele-specific PCR assay reported here, small amounts of DNA extracted from a piece of blood filter paper sample were amplified which produced three different size ranges of diagnostic bands: 650-770 bp PV-species-specific band, 170-230 bp diagnostic band for temperate zone family and 588 bp band for PV type-2. The sizes and patterns of the bands produced by the reference strains were consistent with those of designed target sequences. Of 59 examined isolates from 6 provinces of China, 42 temperate zone family strains, 15 tropical zone family strains and two PV type-2 strains were identified., Conclusion: 1, Three genotype strains of P. vivax mentioned above could be identified by this method with only two rounds of PCR and without probe hybridization. 2, The preliminary results showed that PV type-1 including temperate zone family strains and tropical zone family strains as well as PV type-2 strains are present in China. In addition, another CSP genotype with both sequence characteristics of temperate zone and tropical zone family might also be present in China.

Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is still uncommon. We illustrate four cases where initial bedside attempts at needle aspiration and biopsy of primary and metastatic tumor tissue from the sternum were complicated by inadequate specimen retrieval secondary to marrow necrosis and/or tissue destruction by tumor. In these cases, CT guidance was useful in the precise localization of the bulk of the tissue mass and consequently the successful retrieval of adequate diagnostic specimens. We demonstrate CT guidance as an excellent and convenient alternative in circumstances where adequate marrow aspirations and biopsies are difficult and complicated.

Magnetic resonance imaging has proven to be useful in the diagnosis of spinal cord pathology. Little has been written in the literature concerning magnetic resonance imaging of acute transverse myelitis. A case of magnetic resonance imaging of acute transverse myelitis in a young man with known systemic lupus erythematosus is presented along with a review of the radiographic approach to transverse myelitis.

Dense calcification and psammomatous bodies are common in spinal meningioma, but are rarely reported in osteogenic meningioma. We present a 73-year-old woman with an extramedullary, intradural tumor located at the T5 vertebra. The tumor showed mixed intensity and heterogeneous enhancement on the T1-weighted image and hypointensity on the T2-weighted image, and was situated near the spinal nerve root. The tumor's initial symptom was myelopathy, as is usual with spinal meningioma. We successfully removed the tumor under microscopy and found it to be separated from the vertebral column by the epidural space. The symptoms and signs improved gradually after the operation. Because the pathologic examination revealed areas of lamellar bone with bone marrow in the transitional meningioma, and because these were not related to the psammomatous bodies, osteogenic meningioma was diagnosed. Metaplasia of arachnoid cells is considered to be the putative etiology of osteogenic meningioma.

The distribution of radio-labeled ACNU, MTX and 5-FU in brain and tumor tissue was studied in female Wistar rats by macroautoradiography after intrathecal administration. In normal rats, ACNU and 5-FU, administered intracisternally, distributed rapidly in the subarachnoid space, ventricular system and cerebrospinal fluid (CSF). 5-FU and MTX penetrated the brain deeply; the diffusional transport of ACNU was limited to a depth of 1 or 2 mm from the CSF surface of the brain. MTX and 5-FU clearance into the blood circulation was rather slow while ACNU cleared relatively quickly. The half time of ACNU, 5-FU and MTX radioactivity at the ventricular surface was 10, 21, and 110 min, respectively, at their maximal concentration after intracisternal administration. In rats with leptomeningeal tumor induced by intracisternal inoculation of Walker 256 cells, the distribution patterns of ACNU, 5-FU, and MTX were essentially the same as in normal rats despite 10-20 cell layers of tumor growing in the subarachnoid space. 5-FU and MTX were able to penetrate tumor masses in the subarachnoid space; MTX penetration was slower than that of 5-FU and ACNU failed to penetrate to more than a depth of 1 or 2 mm from the tumor surface.

Nocturnal leg cramps is a common and troublesome problem in elderly individuals, and their etiology is unknown. Treatment with quinine is a common practice, but the effectiveness of the drug is doubtful and adverse drug effects are common. This randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of vitamin B complex capsules (fursulthiamine 50 mg, hydroxocobalamin 250 micrograms, pyridoxal phosphate 30 mg, and riboflavin 5 mg) in 28 elderly patients with hypertension who had severe nocturnal leg cramps that disturbed their sleep. Self-reported ratings of leg cramp frequency, duration, and intensity were used to evaluate severity of nocturnal leg cramps. Both the patients taking vitamin B capsules (n = 14) and those taking placebo (n = 14) received medications three times daily, and were examined regularly at 2-week intervals for 3 months. After 3 months, 86% of the patients taking vitamin B had prominent remission of leg cramps, whereas those taking placebo had no significant difference from baseline. Treatment with vitamin B complex significantly reduced the frequency, intensity, and duration of nocturnal leg cramps. Because quinine is not without potential for side effects, and vitamin B complex is a relatively safe and effective alternative, clinicians should reconsider the treatment of choice for nocturnal leg cramps.

Hemorrhage of juvenile pilocytic astrocytomas is very rare. However, it is clinically important because a high probability of a fatal outcome exists if hemorrhage occurs outside the optic nerve. Hemorrhage of a hypothalamic juvenile pilocytic astrocytoma has been reported only once, from an autopsy examination. We present a successfully managed case. The patient, a 34-year-old man, presented with sudden loss of consciousness. Computed tomography (CT) and magnetic resonance imaging demonstrated an exophytic hypothalamic tumor with a hemorrhage. Craniotomy with total removal of the tumor and the hematoma was performed. Histopathologic examination revealed that the tumor was a juvenile pilocytic astrocytoma. Brain CT examination 18 months later revealed no evidence of tumor recurrence. The patient was well, without neurologic deficit, and had a normal social life as of the last follow-up examination 22 months after craniotomy.

Adhesion molecules play a role in tumor growth, invasiveness, and the metastatic process. The expression of CD44 adhesion molecules in 11 intracranial germinoma specimens was investigated using anti-CD44 monoclonal antibody and immunohistochemical methods. In six of 11 specimens studied, CD44 antibodies were bound to the membrane of tumor cells; in five of six specimens, CD44 antigen was also present in the cytoplasm of tumor cells. The only three patients who showed CD44-positive expression in tumor cells, lymphocytes, and extracellular matrix (ECM) exhibited either cerebrospinal fluid dissemination or multiple tumors at different locations. In all 11 specimens, no expression of CD44 in normal glial cells or capillary endothelium was detected. According to the authors' findings, the expression of CD44 in intracranial germinomas is similar to that of gonadal seminomas. Analysis of the results further suggests the possibility that the expression of CD44 in intracranial germinoma tumor cells, lymphocytes, and ECM may contribute to tumor cell migration, adhesion to cerebrospinal fluid dissemination, and/or multiple tumor locations.

We describe a 53-year-old mother and a her 34-year-old son who suffered from spontaneous subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage due to a ruptured intracranial aneurysm. Diagnosis of the intracranial aneurysm was made by CT scan of the brain, and cerebral angiography. These two cases received surgical intervention and returned to their previous social activity after discharge, even though the mother had arrived in a comatose condition. The literature is reviewed and the characteristic expressions of familial intracranial aneurysms are described. The etiology of cerebral aneurysms is still uncertain but it is likely multifactorial. For the 176 patients with intracranial aneurysm(s) treated at Kaohsiung Medical College Hospital, the mean age at diagnosis was 51.9 years and these aneurysms were distributed mainly at the internal carotid artery (43.8%) and the anterior communicating artery (33.5%). The familial aneurysms tend to rupture at a younger age, occur less often at the anterior communicating artery and more often at the internal carotid artery and the middle cerebral artery as compared with that of non-familial aneurysms. In siblings, aneurysms occur at identical sites or at mirror sites and rupture within the same decade of life twice as frequently as expected in non-familial aneurysm cases. The familial aggregation of intracranial aneurysms and the above characteristic expressions suggest that heredity may play a role in some familial aneurysms. The pattern of inheritance, however, has not been established. Screening examinations and the treatment of unruptured intracranial aneurysms in asymptomatic relatives of the familial cases are also discussed.

We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level.

Intramural coronary artery disease (ICAD) has been reported in myocardium affected with hypertrophic cardiomyopathy (HCM), but has never been studied in detail with respect to the cell type or lipid infiltration involved in the wall-thickening. The lack of heart samples may be one of the rationales to hamper the progress in investigating this disease. Recently, the discovery of naturally occurring HCM in swine has provided an excellent opportunity for the study of ICAD because of the high prevalence of ICAD in this animal. The present study provides a detailed structure feature in the thickened arterial wall of ICAD by both histologic and electron microscopic means. Morphologically, the feature of ICAD is due primarily to the neointimal thickening. Smooth muscle cells (SMC) and extracellular matrix (collagen and elastic fibers) are the major components responsible for the thickened neointima. Fragmentation of the internal elastic membrane is associated with the migration and proliferation of SMC from the media to the intima. Therefore, pigs with HCM may be a potential animal model not only for the study of the mechanism by which SMC migrate and proliferate into intima, but also for the future investigation of interventions in coronary artery occlusion.

Therapeutic efficacy and cell kinetics of intrathecal ACNU, 3-(4-amino-2-methyl-5-pyrimidinyl) methyl-1-(2-chloroethyl)-1-nitrosourea, were investigated in experimental meningeal carcinomatosis rats. Therapeutic effect of intrathecal ACNU (IT ACNU) against meningeal carcinomatosis model was evaluated in rats induced by intracisternal inoculation of Walker 256 carcinosarcoma cells. The median survival time of the rats treated with IT ACNU 1.5 mg/kg on day 5 after tumor inoculation was significantly increased by 145% as compared with that of non-treatment rats. The cell kinetics was studied immunohistochemically using indirect immunoperoxidase method with bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody (Becton-Dickinson). The meningeal carcinomatosis rats were treated with IT ACNU (1.5 mg/kg) on the fifth day after tumor inoculation. Before and 12, 24, 48, 96 or 144 hours after treatment, the rats received intravenous BrdU (200 mg/kg) injection. Thirty minutes later, the rats were sacrificed and the brains were removed. Brain sections were stained immunohistochemically with anti-BrdU monoclonal antibody. Labeling index (LI) which represented the percentage of tumor cells in synthetic phase was obtained by counting immunoreactive cells under the microscope. Before treatment, LI was around 34% on day 5 after tumor inoculation and dropped to below 20% 12 to 48 hours after IT ACNU. However, it increased to around 36% on day 4 after IT ACNU. The antineoplastic effect of IT ACNU against meningeal carcinomatosis rats might be expected in the early stage of intrathecal administration.

Despite modern medical advances, the morbidity and mortality rates associated with spinal epidural abscess remain significant, and the diagnosis is elusive. The incidence of spinal epidural abscess is approximately one to two cases per 10,000 among all patients admitted to hospitals. The symptoms of spinal epidural abscess are varied but include lower back pain, fever, local tenderness and neurological deficit especially in such high risk groups as patients with diabetes, intravenous drug abuse, chronic renal failure, alcoholism, liver disease and immunocompromization. Accumulation of data is difficult in that many physicians will never see a case during their careers. Herein, we present a case with lower back pain associated with both lower legs weakness. His abdomenon CT revealed retroperitonium and right perirenal abscess. External drainage as well as antibiotic treatment was done immediately. However, the lower legs weakness became severe and a lumbar spine MRI revealed T11-L4 epidural abscesses and L2-3 intervertebral space pus formation. Then, the patient was transfered to our Neurosurgical Ward for further treatment. His postoperative condition improved in both lower legs. This case report is to enhance the recognition and treatment of spinal epidural abscess, a rare affliction.

The 90-kDa heat shock protein (HSP90) was purified from porcine brain by a novel single-step purification procedure using diethylaminoethyl high-performance liquid chromatography (HPLC). About 4.8 mg of HSP90 was isolated from 25 g wet wt porcine brain tissue. The purified protein possessed a single moiety on one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining. Western blotting using monoclonal antibody prepared against human HSP90 confirmed its identity as HSP90. These results indicate that small-scale HPLC purification of HSP90 from porcine brain tissue can be readily accomplished, with high yield, using a convenient one-step purification method. The procedure described in this paper represents a significant improvement in current purification methods for the isolation of HSP90 from porcine brain.

Sublytic levels (microM) of hemin destabilized RBC membrane as indicated by ghost fragmentation pattern using a laser viscodiffractometer. Furthermore, electron microscopic study shows that 5 microM of hemin induced echinocytic transformation whereas higher hemin concentration (40 microM) induced spherocytic transformation. In addition, hemin oxidized sulfhydryl groups in a dose dependent fashion and Electron Spin Resonance study suggests that such oxidation may involve a thiyl radical. Moreover, sulfhydryl compounds enhanced hemin-induced lipid peroxidation. Desferroxamine could prevent hemin-induced sulfhydryl oxidation as well as hemin-induced decrease in membrane stability. In contrast, vitamin E could effectively prevent hemin-induced lipid peroxidation but could not prevent hemin-mediated membrane destabilization.