Dramatic band gap reduction incurred by dopant coordination rearrangement in Co-doped nanocrystals of CeO2.

A dramatic band gap narrowing of 1.61 eV has been observed in Co-doped nanocrystals of CeO2 (ceria), as a result of thermal annealing, without changing the ceria crystal structure and the Co concentration. As demonstrated by x-ray absorption fine structures, thermal annealing incurs an oxygen coordination rearrangement around Co atoms from an octahedral coordination to a square-planar coordination. First principle calculation using density functional theory reveals two stable oxygen coordination types surrounding Co, consistent with the experimental observation. The band gap values calculated for the two stable coordination types differ dramatically, reproducing the experimentally observed band gap narrowing. These prominent effects due to local structure rearrangement around dopant atoms can lead to unprecedented methods for band gap engineering in doped nanocrystal oxides.

Triggering receptor expressed on myeloid cells (TREM)-1 participates in Schistosoma mansoni inflammatory responses.

Inflammatory responses to microbial products are amplified by a pathway mediated by triggering a receptor expressed on the myeloid cells (TREM)-1. Relatively a few studies have been performed to investigate the role of TREM-1 in macrophage activation in response to parasitic infection. In this study, we delineate the role of the innate immunoreceptor TREM-1 in the parasite Schistosoma mansoni infection model from early to late (chronic) phases of infection. Flow cytometry analysis revealed gradual increase in the production of TREM-1 protein on CD11b(+) myeloid cells, with maximum production at 5 weeks p.i. Similar results in the pattern of TREM-1 mRNA expressions in splenic CD11b(+) cells from infected mice were obtained by real-time PCR. However, unlike in spleen, the TREM-1 mRNA expression in liver tissue showed no significant increase throughout the infection, including periods of maximum production of parasite eggs. Administration of schistosoma egg homogenate antigen to stimulate J774A.1 cells inhibited TREM-1 expression on the surface, indicating that some substances of the Schistosma eggs may inhibit the expression of TREM-1 on macrophages, lowering the macrophage-mediated inflammatory response of infected hosts.

Generation of a novel factor IX with augmented clotting activities in vitro and in vivo.

BACKGROUND: Hemophilia B is an X-linked inherited disorder caused by the lack of functional factor IX (FIX). Currently, treatment of hemophilia B is performed by intravenous infusion of plasma-derived or recombinant FIX. OBJECTIVE: In an effort to reduce factor usage and cost, we investigated the potential use of FIX variants with enhanced specific clotting activity. METHODS: Seven recombinant FIX variants using alanine replacement were generated and assayed for their activity in vitro and in vivo. RESULTS: One variant containing three substitutions (V86A/E277A/R338A, FIX-Triple) exhibited 13-fold higher specific clotting activity and a 10-fold increased affinity for human FVIIIa compared with FIX-wild-type (FIX-WT) and was thus investigated systematically in vivo. Liver-specific FIX-Triple gene expression following hydrodynamic plasmid delivery revealed a 3.5-fold higher specific clotting activity compared with FIX-WT. Human FIX-Triple and FIX-WT knock-in mice were generated and it was confirmed that FIX-Triple has 7-fold higher specific clotting activity than FIX-WT under normal physiological conditions. Protein infusion of FIX-Triple into hemophilia B mice resulted in greater improvement of hemostasis than that achieved with FIX-WT. Moreover, tail-vein administration of a serotype 8 recombinant Adeno-associated vector (AAV8) expressing either FIX-WT or FIX-Triple in hemophilia B mice demonstrated a 7-fold higher specific clotting activity of FIX-Triple than FIX-WT. CONCLUSIONS: Our results indicate that the FIX-Triple variant exhibits significantly enhanced clotting activity relative to FIX-WT due to tighter binding to FVIIIa, as demonstrated both in vitro and in vivo. Therefore, FIX-Triple is a good candidate for further evaluation in protein replacement therapy as well as gene-based therapeutic strategies.

Up-regulation of a serine-threonine kinase proto-oncogene Pim-1 in oral squamous cell carcinoma.

The Pim-1 proto-oncogene, encoding a serine-threonine kinase, has been found to play an important role in regulating apoptosis, differentiation, proliferation and tumourigenesis. The present study was conducted to assess the importance of Pim-1 in oral tumourigenesis in vivo. Reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to study the expression of Pim-1 in oral squamous cell carcinoma (OSCC) and non-cancerous match tissue (NCMT) sampled from the periphery of the tumours. Pim-1 mRNA expression in OSCC was significantly higher than that in NCMT in 36 tissue pairs (1.33+/-0.41 versus 0.97+/-0.29, P=0.03). The percentage of OSCCs exhibiting strong cytoplasmic Pim-1 immunoreactivity was significantly higher than that of NCMT (60% versus 19%, P=0.007). Pim-1 immunoreactivity is higher in the more differentiated components of a tumour. In around 10% of OSCC cases, Pim-1 immunoreactivity was found in the nucleus as well. These results show novel findings of the up-regulation of Pim-1 expression from NCMT to OSCC. The pathogenetic role of Pim-1 expression in oral tumourigenesis deserves further investigation.

Immunohistochemical and molecular assessment of human herpesvirus type 8 in gastrointestinal tumours.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, histologically identified as highly cellular spindle or epithelioid cell tumours, and often positive for CD34 (60-70%). Kaposi's sarcomas (KSs) are similar to GISTs: they are most often found in the gastrointestinal tract (although cutaneous lesions do occur), they are also composed of spindle or epithelioid cells (although erythrocytes are also seen), and the tumour cells are nearly all positive for CD34. Human herpesvirus type 8 (HHV-8) DNA has been found consistently in all types of KS, in particular in CD34 positive KS tumour cells. However, the association between HHV-8 and GIST has not been investigated. AIMS: To assess the presence of HHV-8 in GISTs. METHODS: Paraffin wax embedded tissues of 86 primary GISTs and their recurrent or metastatic tumours were analysed immunohistochemically for the CD34 antigen and HHV-8 latent nuclear antigen 1 (LNA-1) and by means of the nested polymerase chain reaction (PCR) and real time PCR for HHV-8 DNA. RESULTS: None of the 86 GISTs contained HHV-8 DNA sequences or LNA-1 positive cells. CONCLUSIONS: These results demonstrate the lack of HHV-8 infection in GIST tumour cells. HHV-8 does not appear to play a role in the pathogenesis of GIST, irrespective of the status of the tumour.

Simultaneous multiple hypertensive intracerebral haemorrhages.

BACKGROUND: Simultaneous occurrence of multiple intracerebral haemorrhages (ICHs) in different arterial territories is a rare clinical event which has been reported to be associated with cerebral amyloid angiopathy, venous sinus thrombosis, coagulopathy, vasculitis, haemorrhagic transformation of cerebral infarcts and multiple intracranial pathologies such as vascular anomalies or tumours. Although hypertension is the most common etiological factor for the development of spontaneous single intracerebral bleeding, its role in simultaneous multiple ICHs is not clear. METHODS: The authors have reviewed all patients with non-traumatic ICH admitted to Kaohsiung Medical University Hospital from 1993 to 2002. Ten hypertensive patients with simultaneous multiple ICHs were found. For the purpose of comparison, another 600 cases with solitary hypertensive ICH were also reviewed as a control group. Computerized tomographic scans and medical records concerning patients' histories, clinical presentations, locations of haematomas, associated risk factors, and outcome were analyzed. FINDINGS: The mean age and sex distribution were similar in both patient groups. Bilateral putaminal or thalamic haemorrhages were the most common combinations of simultaneous bleedings. As for the individual location of haematoma, there was a strong preponderance for the supratentorial space with the thalamus being the most preferable site. The duration of hypertension was longer and the percentage of previous stroke was higher in patients with multiple ICHs. Other associated risk factors were similar in both groups except for higher incidence of hypercholesterolemia in multiple ICHs group. Patients with simultaneous multiple ICHs had a much worse outcome compared to those with solitary ICH. CONCLUSIONS: As with solitary ICH, hypertension is still the most important etiological factor for simultaneous multiple ICHs. The widespread and prolonged degeneration of intracerebral arterioles predispose patients to the development of multiple ICHs, which could be justified by the longer history of hypertension and higher incidence of former strokes. Only hypercholesterolemia was identified to be significantly associated with this unusual brain event in our study. The mechanism underlying the development of simultaneous multiple ICHs is not clear although structural and haemodynamic changes of first haemorrhage may be responsible for the second one. Poorer outcome in patients with multiple ICHs can be explained by the concomitant destruction of crossing and non-crossing fiber tracts and bilateral diaschisis phenomenon.

In vitro anti-inflammatory effects of quercetin 3-O-methyl ether and other constituents from Rhamnus species.

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-alpha ( TNF-alpha) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-alpha formation in LPS/IFN-gamma (interferon-gamma)-stimulated murine microglial cell lines N9.

Association analysis of a functional G protein beta3 subunit gene polymorphism (C825T) in mood disorders.

The guanine nucleotide-binding proteins (G proteins), heterotrimers consisting of alpha, beta and gamma subunits, convey signals initiated by the activation of many neurotransmitter receptors. Evidence for involvement of the G proteins in mood disorders relies on the effects of mood stabilizers and antidepressants on G protein function. In addition, abnormalities in the expression of G proteins have been demonstrated in mood disorder patients. Therefore, we tested the hypothesis that a functional polymorphism (C825T) in the G protein beta3 gene subunit (GNB3) confers susceptibility to mood disorders. A population-based association study was utilized, and GNB3 was genotyped for 144 mood disorder patients and 153 normal controls. The results reveal that it is not likely that the C825T polymorphism in the GNB3 gene subunit is involved in mood disorder pathogenesis. Further studies of the associations between other G protein subunits and mood disorder are needed to fully elaborate the involvement of this protein in mood disorders.

Primary cerebral anaplastic large cell lymphoma containing abundant reactive histiocytes and eosinophils. A case report and literature review.

Primary cerebral anaplastic large cell lymphoma (ALCL) is very rare. We report on our experience with such a case and review the literature. A 46-year-old Taiwanese woman presented with headache, weakness of her right extremity, and limited eye movement. A solid mass (5 cm x 4 cm) at the left occipital lobe was almost completely removed. The neoplastic cells, some of which had reniform or embryo-like nuclei, were large and were admixed with abundant eosinophils, histiocytes, and some small lymphocytes. These neoplastic cells expressed CD30, CD43, granzyme B and T-cell intracellular antigen-1, but not ALK1, CD3, CD20, CD45, CD79a, cytokeratin, and EMA. They were positive for Epstein-Barr virus-encoded mRNA by in situ hybridization. Polymerase chain reaction study of formalin-fixed tissue showed a clonal gene arrangement of the T-cell receptor-gamma chain. ALCL of T-cell lineage with cytotoxic phenotype was diagnosed. The patient received cranial irradiation and has remained with no evidence of disease for 25 months of follow-up.

Characterization of serum and urinary chromogranin A by size exclusion chromatography: impact on calibrator selection and urinary assay.

Serum chromogranin A (CgA) is a useful marker for neuroendocrine tumors and is detectable in carcinomas at advanced stages. Elevated serum CgA is also an indicator of poor prognosis in prostate cancer and is useful for predicting the failure of hormonal therapy for prostate cancer patients. We found that CgA molecules with three different sizes could be detected in normal human serum. However, only the largest CgA molecule appears in patients with liver disease. Serum taken from cancer patients is composed predominantly of the middle-sized molecule, whereas the smallest CgA molecule was elevated in serum drawn from renal patients. Moreover, only the smallest CgA molecule was found in urine. We believe that the largest CgA molecule is metabolized by the liver, whereas the smallest CgA molecule is removed from the blood circulation via the kidney. Because the medium-sized CgA is the dominant molecule in both the cell medium of the tumor cell line SK-N-AS and sera from patients with malignant diseases, CgA from the cell medium was selected as the calibrator for the CgA ELISA assay. Our findings also suggest that it would not be possible to measure the urinary CgA to reflect the serum CgA concentration in order to detect pheochromocytoma among patients with hypertension.

Inhibitory effect of DCDC on lipopolysaccharide-induced nitric oxide synthesis in RAW 264.7 cells.

In the present study we have examined the effect of DCDC (2',5'-dihydroxy-4-chloro-dihydrochalcone) on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to DCDC inhibited the nitrite accumulation in culture medium. DCDC also concentration-dependently inhibited LPS-stimulated increase of iNOS expression; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory action to DCDC is mainly due to the inhibition on iNOS expression rather than iNOS enzyme activity. DCDC significantly inhibited LPS-evoked degradation of IkappaB-alpha and the nuclear translocation of NF-kappaB; it also exhibited the activity of scavenging the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). DCDC also inhibited cyclooxygenase-2 activity in RAW 264.7 cells with an IC50 of 3.0 microM; furthermore, it also significantly decreased LPS-induced mortality rate in mice. Taken together, we demonstrate that DCDC exhibits inhibitory effects on nitric oxide production through the inhibition of IkappaB-alpha degradation and NF-kappaB activation, and therefore the suppression of iNOS expression. DCDC also shows the antioxidant activity and COX-2 inhibitory action. Moreover, it improves survival in a murine model of endotoxaemia suggesting that DCDC may be potential in the therapy of septic shock.

Bioactive constituents of the roots of Cynanchum atratum.

A novel biphenylneolignan, 2,6,2',6'-tetramethoxy-4,4'-bis(2,3-epoxy-1-hydroxypropyl)biphenyl (1), and two new glycosides named atratoglaucosides A (2) and B (3), were isolated from the roots of Cynanchum atratum, and their structures were determined on the basis of chemical and spectroscopic evidence. The aglycons of 2 and 3 were identified as glaucogenin C and 7-desoxyneocynapanogenin A, a new disecopregnane. A known compound, glaucogenin C 3-O-beta-D-cymaropyranosyl-(1-->4)-alpha-L-diginopyranosyl-(1-->4)-beta-D-thevetopyranoside (4), isolated from the same source, showed a significant cytotoxic effect against 212 cells. This substance also gave a significant inhibitory effect on TNF-alpha (tumor necrosis factor-alpha) formation from the RAW 264.7 mouse macrophage-like cell line stimulated with LPS (lipopolysaccharide) and on the N9 microglial cell line stimulated with LPS/IFN-gamma (interferon-gamma).

Uterine leiomyoma with massive lymphocytic infiltration simulating malignant lymphoma. A case report with immunohistochemical study showing that the infiltrating lymphocytes are cytotoxic T cells.

Uterine leiomyoma with massive lymphoid infiltration is very rare and may simulate malignant lymphoma. To the best of our knowledge, this is the first description of such a lesion occurring in an Oriental, and the ninth case in the English literature. A 50-year-old Taiwanese woman had urinary frequency and nocturia because of a uterine myoma. The myomectomy specimen was identified as a well-defined tumor, 6.5-cm in diameter, the cut surface of which was pale, white and whorled. A massive lymphocytic infiltration accompanied by plasma cells and histiocytes was noted in the leiomyoma but not in the surrounding non-neoplastic myometrial fibers. Most infiltrating lymphocytes were positive for CD3 and T cell intracellular antigen-1, a cytotoxic marker. The postoperative course was uneventful, and the urinary symptoms improved within a 6-month follow-up period.

Synthesis, antiplatelet and vasorelaxing effects of monooxygenated flavones and flavonoxypropanolamines.

A series of flavones and flavonoxypropanolamines were synthesized and tested in-vitro for their ability to inhibit aggregation of washed rabbit platelets and human platelet-rich plasma (PRP), and for vasoconstriction of rat thoracic aorta. The various substituted positions of the hydroxyl group in flavone ring B and the various oxypropanolamine side chains substituted at position C-2' of flavone modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline (epinephrine), suggesting that the antiplatelet effect of these compounds is mainly due to an inhibitory effect on thromboxane formation. Compounds 11 and 12 also had potent vasorelaxant effects in rat thoracic aorta. Phenylephrine- and high-K+-induced 45Ca2+ influx in aorta were both inhibited by the selected compound 11. This result indicates that the inhibitory effect of 11 on the contractile response caused by high-K+ medium and noradrenaline (norepinephrine) in rat thoracic aorta is mainly due to inhibition of Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels.

Undifferentiated ovarian carcinoma associated with leukemoid reaction.

Exceptionally excess leukocytosis or leukemoid reaction may develop in association with carcinomas of the lung and stomach. The authors describe a 72-year-old lady with FIGO stage III ovarian undifferentiated carcinoma who presented with fever and abdominal pain. Her serial WBC counts were up to 143,000/microl with elevated leukocyte alkaline phosphatase score. She received extended total hysterectomy, left salpingo-oophorectomy, and de-bulking of the retroperitoneal mass. Her left ovarian cancer was composed of diffuse sheets of large undifferentiated cells that were immunoreactive for cytokeratin, confirming the epithelial nature. She passed away one week after operation and five weeks after presentation without autopsy. This is the first report of ovarian cancer associated with leukemoid reaction in the English literature.

Anticancer activity evaluation of the solanum glycoalkaloid solamargine. Triggering apoptosis in human hepatoma cells.

Solamargine, an herbal and molluscicidal medicine derived from Solanum incanum, is a steroidal alkaloid glycoside. To characterize the anticancer mechanism of solamargine on human hepatoma cells (Hep3B), changes of cell morphology, DNA content, and gene expression of cells after solamargine treatment were studied. The appearance in solamargine-treated cells of chromatin condensation, DNA fragmentation, and a sub-G(1) peak in a DNA histogram suggests that solamargine induces cell death by apoptosis. The maximum number of dead Hep3B cells was detected within 2 hr of incubation with constant concentrations of solamargine, and no further cell death was observed after an extended incubation with solamargine, indicating that the action of solamargine was irreversible. To determine the susceptibility of cell phases to solamargine-mediated apoptosis, Hep3B cells were synchronized at defined cell cycles by cyclosporin A, colchicine, and genistein, followed by solamargine treatment. The IC(50) values of solamargine for control, G(0)/G(1)-, M-, and G(2)/M-synchronized Hep3B cells were 5.0, > 10, 3.7, and 3.1 microg/mL, implying that cells in the G(2)/M phases are relatively susceptible to solamargine-mediated apoptosis. In addition, a parallel up-regulation of tumor necrosis factor receptor (TNFR)-I and -II on Hep3B cells was detected after solamargine treatment, and the solamargine-mediated cytotoxicity could be neutralized with either TNFR-I or -II specific antibody. Therefore, these results reveal that the actions of TNFR-I and -II on Hep3B cells may be independent, and both are involved in the mechanism of solamargine-mediated apoptosis.

New lignan glycosides with potent antiinflammatory effect, isolated from Justicia ciliata.

Two new lignan glycosides, 4-O-[alpha-L-arabinopyranosyl-(1' "-->2' ')-beta-D-xylopyranosyl-(1' " '-->5' ')-beta-D-apiofuranosyl]diphyllin (1), named ciliatoside A (1), and 4-O-¿[beta-D-apiofuranosyl-(1' " "-->3' ")-alpha-L-arabinopyranosyl-(1' "-->2' ')][beta-D-xylopyranosyl-(1' " '-->5' ')]-beta-D-apiofuranosyl¿diphyllin (2), named ciliatoside B (2), were isolated from the whole plant of Justicia ciliata. The structures of 1 and 2 were determined by spectral and chemical methods. Compounds 1 and 2 strongly inhibited the accumulation of NO(2)(-) in lipopolysaccharide-stimulated RAW 264.7 cells in a concentration-dependent manner with IC(50) values of 27.1 +/- 1.6 and 29.4 +/- 1.4 microM, respectively.

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms.

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.

Chronic focal encephalitis (Rasmussen's syndrome) in an adult.

Chronic focal encephalitis in adults is rare. Here we report a case of chronic focal encephalitis with epilepsy in a man. A 53-year-old man was admitted to our hospital because of right-sided focal seizures and epilepticus partialis continua. Brain imaging studies demonstrated progressive, focal, left cerebral atrophy. Prominent degenerative changes including neuronal loss and astrocytic gliosis were found on brain biopsy. Although the characteristics were typical of Rasmussen's encephalitis, unlike chronic focal encephalitis in children, his seizures were easily controlled by traditional antiepileptic therapy.