Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Papillary ependymoma is a rare variant of ependymoma and often gives rise to confusion with choroid plexus papilloma because of topographic, light microscopic and ultrastructural similarities. Here, we report two cases of papillary ependymomas regarding their unique clinicopathologic features and differential points from choroid plexus papilloma. Brain MRI revealed a large mass in the left lateral ventricle in one case and a 3cm sized mass in the pineal area and the 3rd ventricle in the other. Microscopically, the tumor was characterized by papillary and tubular structures. Immunohistochemically, the tumor cells in both cases expressed cytokeratins(CK22 and CAM 5.2) but did not express glial fibrillary acidic protein(GFAP), vimentin, epithelial membrane antigen, and S100 protein. This is a very unusual immunohistochemical feature for papillary ependymoma. Ultrastructurally, the tumor showed a mosaic pattern of tumor cells with frequent intercellular microrosettes having a few stubby microvilli, a few cilia and zonulae adherentes. The cytoplasmic processes were markedly reduced compared to conventional ependymoma. The cytoplasm did not contain intermediate filaments. Interestingly, the mitochondria showed abnormal features with a pleomorphic shape and abnormal cristae in both cases. These ultrastructural features enabled differentiation between papillary ependymoma and choroid plexus papilloma in addition to the light microscopic findings.
Inclusion body myositis is a rare myopathy that clinically resembles a chronic polymyositis and histopathologically is characterized by the presence of rimmed vacuoles containing ultrastructural cytoplasmic degradation products with filamentous intranuclear and cytoplasmic inclusions. Since clinical features are not uniform, histopathologic and ultrastructural studies are necessary to confirm the diagnosis. We report a typical case of inclusion body myositis with histopathologic and ultrastructural study. The patient was a 31 year old male who presented with progressive weakness of both forearms, hands and lower extremities for 10 years.
A case of spinal meningeal melanocytoma is reported along with clinicopathologic, immunohistochemical and ultrastructural studies. This patient presented clinically with paraparesis, tingling sensation and numbness of both lower extremities of 4 months duration. No mucocutaneous pigmented nevi were found. On operation, scattered coal-black pigmented lesions were found in the meninges between T3 and T4-5 interspace level. Nearly total removal was carried out. The tumor was composed of spindle and epithelioid cells with heavy brown-black pigmentation. There was no pleomorphism, mitosis, hemorrhage, necrosis or invasion to the underlying cord tissue. In Korea, this case appears to be the first example of this disease. Neurologic deficit improved after surgical excision.
We have recently found a high prevalence of non-typeable pneumococcal isolates (NTPn) circulating in day-care centers in Central Brazil, besides serotype 14 isolates. We therefore examined the genetic relationship among NTPn and serotype 14 from carriage and invasive pneumococcal isolates obtained from children attending emergency rooms enrolled in a population-based surveillance.
The isolates were characterized by Quellung reaction serotyping, PCR for the presence of pneumolysin and the loci for a capsule gene (cpsA) and the type 14 gene (cps14H) in all NTPn, and by multilocus sequence typing and pulsed field gel electrophoresis.
87.2% of the isolates were clustered into nine clusters. The major cluster included 41 pneumococcal serotype 14 (28 carriage and 13 invasive isolates) and two NTPn related to the global pneumococcal clone Spain 9V-3. Overall, 95.4% of the NTPn carriage strains were genetically related to carriage or invasive strains expressing serotype 14. A dominant NTPn lineage was found, that grouped 14 pneumococcal strains. Almost half of the multidrug-resistant isolates grouped into the NTPn cluster.
These findings provide baseline data to assess the impact of the pneumococcal vaccination on the molecular epidemiology of S. pneumoniae. Changes in frequency of NTPn isolates and also genetic changes should be carefully monitored post vaccination, to detect potential vaccine-escape or replacement disease by capsule switched strains, especially in areas where colonization with NTPn has been frequently observed.
molecular epidemiology; non-typeable Streptococcus pneumoniae; carriage; invasive pneumococcal disease
To investigate serial changes of the Ahmed glaucoma valve (AGV) implant tube in the anterior chamber by anterior segment optical coherence tomography (AS-OCT).
Patients who had received AGV implantation without complications (n=48) were included in this study. Each patient received follow-up examinations including AS-OCT at days 1 and 2, week 1, and months 1, 3, 6, and 12. Tube parameters were defined to measure its length and position. The intracameral length of the tube was from the tip of the bevel-edged tube to the sclerolimbal junction. The distance between the extremity of the tube and the anterior iris surface (T–I distance), and the angle between the tube and the posterior endothelial surface of the cornea (T–C angle) were defined. Factors that were related to tube parameters were analysed by multiple regression analysis.
The mean change in tube length was −0.20±0.17 mm, indicating that the tube length shortened from the initial inserted length. The mean T–I distance change was 0.11±0.07 mm and the mean T–C angle change was −6.7±5.6°. Uveitic glaucoma and glaucoma following penetrating keratoplasty showed the most changes in tube parameters. By multiple regression analysis, diagnosis of glaucoma including uveitic glaucoma (P=0.049) and glaucoma following penetrating keratoplasty (P=0.008) were related to the change of intracameral tube length.
These results suggest that the length and position of the AGV tube changes after surgery. The change was prominent in uveitic glaucoma and glaucoma following penetrating keratoplasty.
Ahmed glaucoma valve; anterior segment optical coherence tomography; glaucoma surgery
The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of breast cancer with prognostic factors.
335 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) and ductal carcinoma in situ (DCIS) who underwent breast MRI with diffusion-weighted imaging were included in this study. ADC of breast cancer was calculated using two b factors (0 and 1000 s mm–2). Mean ADCs of IDC NOS and DCIS were compared and evaluated. Among cases of IDC NOS, mean ADCs were compared with lymph node status, size and immunochemical prognostic factors using Student's t-test. ADC was also correlated with histological grade using the Kruskal–Wallis test.
Mean ADC of IDC NOS was significantly lower than that of DCIS (p<0.001). However, the mean ADC of histological grade of IDC NOS was not significantly different (p=0.564). Mean ADC of oestrogen receptor (ER)-positive or progesterone receptor (PR)-positive cancer was significantly lower than that of ER-negative or PR-negative cancer (p=0.003 vs
p=0.032). Mean ADC of Ki-67 index-positive cancer was significantly lower than that of Ki-67 index-negative cancer (p=0.028). Mean ADC values of cancers with increased microvascular density (MVD) were significantly lower than those of cancer with no MVD increase (p=0.009). No correlations were observed between mean ADC value and human growth factor receptor 2 expression, tumour size and lymph node metastasis.
Low ADC value was correlated with positive expression of ER, PR, increased Ki-67 index, and increased MVD of breast cancer.
Serogroup 6 of Streptococcus pneumoniae contains three serotypes named 6A, 6B and 6C with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyl transferase, which has been replaced with a glucosyl transferase in the 6C capsule gene locus. We considered that a new serotype named “6X1” would be possible if the galactosyl transferase of the 6B capsule gene locus is replaced with the glucosyl transferase of 6C. We demonstrate that this gene transfer yields a viable pneumococcal strain and the capsular polysaccharide from this strain has the predicted chemical structure and serologic similarity to the capsular polysaccharide of the 6B serotype. The new strain (i.e., serotype 6X1) is typed as 6B by the quellung reaction but it can be distinguished from 6B strains with monoclonal antibodies to 6B polysaccharide. Reexamination of 264 pneumococcal isolates that were previously typed as 6B with classical typing methods revealed no isolates expressing serotype 6X1. Nevertheless, this study shows this capsular polysaccharide is biochemically possible and could exist/emerge in nature.
pneumococcus; serotype; vaccine
The aim of this study was to evaluate the success rate in ultrasonography-guided ethanol ablation (EA) of benign, predominantly solid thyroid nodules and to assess the value of colour Doppler ultrasonography in prediction of its success.
From January 2008 to June 2009, 30 predominantly solid thyroid nodules in 27 patients were enrolled. Differences in the success rate of EA were assessed according to nodule vascularity, nodule size, ratio of cystic component, amount of injected ethanol, degree of intranodular echo-staining just after ethanol injection and the number of EA sessions.
On follow-up ultrasonography after EA for treatment of thyroid nodules, 16 nodules showed an excellent response (90% or greater decrease in volume) and 2 nodules showed a good response (50–90% decrease in volume) on follow-up ultrasonography. However, 5 nodules showed an incomplete response (10–50% decrease in volume) and 7 nodules showed a poor response (10% or less decrease in volume). Statistical analysis revealed a significant association of nodule vascularity (p = 0.002) and degree of intranodular echo-staining just after ethanol injection (p = 0.003) with a successful outcome; however, no such association was observed with regard to nodule size, ratio of cystic component, amount of infused ethanol and the number of EA sessions. No serious complications were observed during or after EA.
The success rate of EA was 60%, and nodule vascularity and intranodular echo-staining on colour Doppler ultrasonography were useful in predicting the success rate of EA for benign, predominantly solid thyroid nodules.
Docetaxel is widely used as a chemotherapeutic agent for gastric cancer treatment. A
combined regimen with sunitinib demonstrated a synergistic antitumour effect in a
preclinical model. The aim of this study was to evaluate the efficacy and safety of this
combination in patients with unresectable or metastatic advanced gastric cancer
following failure of treatment with a fluoropyrimidine and platinum combination.
This open-label, phase II, randomised trial enrolled patients with unresectable or
metastatic gastric cancer. Patients were assigned to either a docetaxel monotherapy arm
(D only arm: 60 mg m−2, every 3 weeks) or a combination
arm (DS arm: docetaxel+sunitinib 37.5 mg every day). The primary end point
of the study was time to progression and the secondary end points were overall response
rate, disease control rate, overall survival, and toxicity profile. A pharmacokinetic
study was also performed.
A total of 107 patients were entered into the study. The TTP was not significantly
prolonged in the DS arm when compared with the D only arm (DS vs D only arm:
3.9 months (95% confidence interval (CI) 2.9–4.9) vs 2.6 months
(95% CI 1.8–3.5) (P=0.206). The hazard ratio for TTP was
0.77 (95% CI 0.52–1.16). However, the objective response rate was
significantly higher in the DS arm (41.1% vs 14.3%,
P=0.002). Patients in the DS arm experienced stomatitis, diarrhoea, and
hand–foot syndrome more frequently.
The addition of sunitinib to docetaxel did not significantly prolong TTP, although it
significantly increased response.
gastric cancer; second-line chemotherapy; docetaxel; sunitinib
Correlative light and electron microscopy promises to combine molecular specificity with nanoscale imaging resolution. However, there are substantial technical challenges including reliable co-registration of optical and electron images, and rapid optical signal degradation under electron beam irradiation. Here, we introduce a new approach to solve these problems: imaging of stable optical cathodoluminescence emitted in a scanning electron microscope by nanoparticles with controllable surface chemistry. We demonstrate well-correlated cathodoluminescence and secondary electron images using three species of semiconductor nanoparticles that contain defects providing stable, spectrally-distinguishable cathodoluminescence. We also demonstrate reliable surface functionalization of the particles. The results pave the way for the use of such nanoparticles for targeted labeling of surfaces to provide nanoscale mapping of molecular composition, indicated by cathodoluminescence colour, simultaneously acquired with structural electron images in a single instrument.
This study was performed in order to verify bifid mandibular canals revealed from panoramic radiographic results.
1000 panoramic radiographs from dental patients and the panorama, cone beam CT (CBCT) and micro-CT from 40 dry mandibles were examined for bifid mandibular canals. The results were confirmed by a stereoscopic and histological examination of the cross-sectioned mandibles.
The prevalence of bifid canals detected from the panoramic radiographs was 0.038. The panoramic radiographs from one dry mandible showed two separate radiolucent mandibular canal-like structures delineated by radio-opaque lines. However, a stereoscopic and histological examination of a cross-section of the mandible showed that only one canal was a true canal containing neurovascular bundles: the other was false, reflecting merely a bony trabecular pattern.
The presence of bifid mandibular canals determined by panoramic radiography should be judged with great caution in relation to dental surgery.
bifid canals; panorama; micro-CT; cone beam computed tomography; inferior alveolar nerve
Cytomegalovirus (CMV) ventriculoencephalitis is a rare but serious potential complication of CMV infection in immunocompromised patients. Characteristic diffusion-weighted imaging findings can be helpful for the diagnosis of CMV ventriculitis, as in this case report.
The aims of this study were to develop detailed clinical models (DCMs) for nursing problems related to perinatal care and to test the applicability of these detailed clinical models.
First, we extracted entities of nursing problems by analyzing nursing-problem statements from nursing records, reviewing the literature, and interviewing nurse experts. Second, we extracted attributes and possible values needed to describe the entities in more detail by again analyzing nursing statements, reviewing the literature, and consulting nurse experts. Third, DCMs were modeled by linking each entity with possible attributes with value sets and optionalities. Fourth, entities, attributes and value sets in the DCMs were mapped to the International Classification for Nursing Practice (ICNP) version 2. Finally, DCMs were validated by consulting a group of experts and by applying them to real clinical data and nursing care scenarios published in the literature. The adequacy of the entities, attributes, value sets, and optionalities of the attributes were validated.
Fifty-eight entities were identified, 41 entities from nursing records, 12 entities from literature review and 5 entities from nurse experts. Sixty-five attributes with values were identified, 25 attributes from nursing records, 34 attributes from literature review, and 6 attributes from nurse experts. In total 58 DCMs were developed and validated.
The DCMs developed in this study can ensure that electronic health records contain meaningful and valid information, and support the semantic interoperability of nursing information.
Information sharing, model, standards; data collection; knowledge representation
Tandemly repeated DNAs, referred to as satellite DNAs, often occur in a genome in a genus-specific manner. However, the mechanisms for generation and evolution for these sequences are largely unknown because of the uncertain origins of the satellite DNAs. We found highly divergent genus-specific satellite DNAs that showed sequence similarity with genus-specific intergenic spacers (IGSs) in the family Solanaceae, which includes the genera Nicotiana, Solanum and Capsicum. The conserved position of the IGS between 25S and 18S rDNA facilitates comparison of IGS sequences across genera, even in the presence of very low sequence similarity. Sequence comparison of IGS may elucidate the procedure of the genesis of complex monomer units of the satellite DNAs. Within the IGS of Capsicum species, base substitutions and copy number variation of subrepeat monomers were causes of monomer divergence in IGS sequences. At the level of inter-generic IGS sequences of the family Solanaceae, however, genus-specific motif selection, motif shuffling between subrepeats and differential amplification among motifs were involved in formation of genus-specific IGS. Therefore, the genus-specific satellite DNAs in Solanaceae plants can be generated from differentially organized repeat monomers of the IGS rather than by accumulation of mutations from pre-existent satellite DNAs.
Solanaceae; genus specific; satellite DNA; intergenic spacer (IGS)
Rubus coreanus fruits have been employed as a traditional medicine for centuries in the Asia-Pacific region. Its pharmacological action differs according to the different extraction methods utilized and the degree of fruit ripening. In this study, we determined the cellular effect of different ethanol extracts of mature and immature Rubus coreanus fruits in human hepatic cell line, HepG2 cells. The antioxidant activity, effect on superoxide dismutase activity and cholesterol biosynthesis efficiency was also evaluated. Immature Rubus coreanus extract showed higher antioxidant capability, compared with that of its mature fractions. Cellular antioxidant proteins including HO-1, Cu/Zn-superoxide dismutase and catalase were highly expressed in the presence of Rubus coreanus. Cholesterol levels in HepG2 cells treated with the water fraction of immature Rubus coreanus were significantly reduced. This antihyperlipidaemic action of Rubus coreanus is a consequence of cholesterol biosynthesis and extracellular secretion in HepG2 cells. These results indicate that among different ethanol fraction of mature and immature Rubus coreanus fruit extracts, water extract of immature fruit extract shows higher antioxidant as well as higher antihyperlipidaemic action.
Antioxidant; antihyperlipidaemic; cholesterol; bokbunza; Rubus coreanus
Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation.
retinal ganglion cell; glaucoma; autophagy
Multi-layered poly(glycerol sebacate) (PGS) scaffolds with controlled pore microarchitectures were fabricated, combined with heart cells, and cultured with perfusion to engineer contractile cardiac muscle constructs. First, one-layered (1L) scaffolds with accordion-like honeycomb shaped pores and elastomeric mechanical properties were fabricated by laser microablation of PGS membranes. Second, two-layered (2L) scaffolds with fully interconnected three dimensional pore networks were fabricated by oxygen plasma treatment of 1L scaffolds followed by stacking with off-set laminae to produce a tightly bonded composite. Third, heart cells were cultured on scaffolds with or without interstitial perfusion for 7 days. The laser-microablated PGS scaffolds exhibited ultimate tensile strength and strain-to-failure higher than normal adult rat left ventricular myocardium, and effective stiffnesses ranging from 220 to 290 kPa. The 7 day constructs contracted in response to electrical field stimulation. Excitation thresholds were unaffected by scaffold scale up from 1L to 2L. The 2L constructs exhibited reduced apoptosis, increased expression of connexin-43 (Cx-43) and matrix metalloprotease-2 (MMP-2) genes, and increased Cx-43 and cardiac troponin-I proteins when cultured with perfusion as compared to static controls. Together, these findings suggest that multi-layered, microfabricated PGS scaffolds may be applicable to myocardial repair applications requiring mechanical support, cell delivery and active implant contractility.
We report three cases of eosinophilic cystitis. Contrast-enhanced computed tomography (CT) revealed characteristic bladder wall thickening exceeding 10 mm, with preservation of the mucosal lining and intense, progressive contrast enhancement on sequential arterial and delayed scans. Eosinophilic cystitis might have been associated with eosinophilic infiltration in other organs, such as the gastrointestinal tracts and liver.
The aim of this study was to determine the differences in CT findings of miliary tuberculosis in patients with and without HIV infection. Two radiologists reviewed retrospectively the CT findings of 15 HIV-seropositive and 14 HIV-seronegative patients with miliary tuberculosis. The decisions on the findings were reached by consensus. Statistical analysis was performed using the χ2 test, Mann–Whitney U-test and Fisher's exact test. All of the HIV-seropositive and -seronegative patients had small nodules and micronodules distributed randomly throughout both lungs. HIV-seropositive patients had a higher prevalence of interlobular septal thickening (p = 0.017), necrotic lymph nodes (p = 0.005) and extrathoracic involvement (p = 0.040). The seropositive patients had a lower prevalence of large nodules (p = 0.031). In conclusion, recognition of the differences in the radiological findings between HIV-seropositive and -seronegative patients may help in the establishment of an earlier diagnosis of immune status in patients with miliary tuberculosis.
Black rice is rich in anthocyanin and is expected to have more healthful dietary potential than white rice. We assessed expression of anthocyanin in black rice cultivars using a newly designed 135 K Oryza sativa microarray. A total of 12,673 genes exhibited greater than 2.0-fold up- or down-regulation in comparisons between three rice cultivars and three seed developmental stages. The 137 transcription factor genes found to be associated with production of anthocyanin pigment were classified into 10 groups. In addition, 17 unknown and hypothetical genes were identified from comparisons between the rice cultivars. Finally, 15 out of the 17 candidate genes were verified by RT-PCR analysis. Among the genes, nine were up-regulated and six exhibited down-regulation. These genes likely play either a regulatory role in anthocyanin biosynthesis or are related to anthocyanin metabolism during flavonoid biosynthesis. While these genes require further validation, the results here underline the potential use of the new microarray and provide valuable insight into anthocyanin pigment production in rice.
Anthocyanin; Black rice; Pigmentation; Rice microarray; Transcription factor
The interest in registering a set of images has quickly risen in the field of medical image analysis. Mutual information (MI) based methods are well-established for pairwise registration but their extension to higher dimensions (multiple images) has encountered practical implementation difficulties. We extend the use of alpha mutual information (αMI) as the similarity measure to simultaneously register multiple images. αMI of a set of images can be directly estimated using entropic graphs spanning feature vectors extracted from the images, which is demonstrated to be practically feasible for joint registration.
In this paper we are specifically interested in monitoring malignant tumor changes using simultaneous registration of multiple interval MR or CT scans. Tumor scans are typically a decorrelating sequence due to the cycles of heterogeneous cell death and growth. The accuracy of joint and pairwise registration using entropic graph methods is evaluated by registering several sets of interval exams. We show that for the parameters we investigated simultaneous joint registration method yields lower average registration errors compared to pairwise. Different degrees of decorrelation in the serial scans are studied and registration performance suggests that an appropriate scanning interval can be determined for efficiently monitoring lesion changes. Different levels of observation noise are added to the image sequences and the experimental results show that entropic graph based methods are robust and can be used reliably for multiple image registration.