Deshima 2.0: Rapid Redshift Surveys and Multi-line Spectroscopy of Dusty Galaxies.

We present a feasibility study for the high-redshift galaxy part of the Science Verification Campaign with the 220-440 GHz deshima 2.0 integrated superconducting spectrometer on the ASTE telescope. The first version of the deshima 2.0 chip has been recently manufactured and tested in the lab. Based on these realistic performance measurements, we evaluate potential target samples and prospects for detecting the [CII] and CO emission lines. The planned observations comprise two distinct, but complementary objectives: (1) acquiring spectroscopic redshifts for dusty galaxies selected in far-infrared/mm-wave surveys; (2) multi-line observations to infer physical conditions in dusty galaxies.

CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS.

BACKGROUND: Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids. MATERIALS AND METHODS: Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels. RESULTS: Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia. CONCLUSION: From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

Gas filaments of the cosmic web located around active galaxies in a protocluster.

Cosmological simulations predict that the Universe contains a network of intergalactic gas filaments, within which galaxies form and evolve. However, the faintness of any emission from these filaments has limited tests of this prediction. We report the detection of rest-frame ultraviolet Lyman-α radiation from multiple filaments extending more than one megaparsec between galaxies within the SSA22 protocluster at a redshift of 3.1. Intense star formation and supermassive black-hole activity is occurring within the galaxies embedded in these structures, which are the likely sources of the elevated ionizing radiation powering the observed Lyman-α emission. Our observations map the gas in filamentary structures of the type thought to fuel the growth of galaxies and black holes in massive protoclusters.

A dominant population of optically invisible massive galaxies in the early Universe.

Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light1. However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs2-4, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10-5 per cubic megaparsec (two orders of magnitude higher than extreme starbursts5) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.

Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

The gravitationally unstable gas disk of a starburst galaxy 12 billion years ago.

Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction of the new stars form in the central kiloparsec of the galaxy1-3, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history4 and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies5.

Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention.

OBJECTIVE: Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. METHOD: A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. RESULTS: There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. CONCLUSION: The present findings suggest a possibility that 5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

Y-box binding protein 1 expression in gastric cancer subtypes and association with cancer neovasculature

Purpose. Y-box binding protein 1 (YB-1) expression in cancer cells is closely associated with malignant progression and poor prognosis in various cancers. Recently, we demonstrated that YB-1 expression in cancer cells is an immunomarker for patient prognosis and liver metastasis of gastric cancer (GC), and identified YB-1 as an excellent biomarker of angiogenic and proliferating endothelial cells in cancers. We further explored the expression patterns of YB-1 in gastric vasculature and the relationship with the clinical pathologic characteristics, as well as YB-1 phenotype in cancer cells. Methods/Patients. Immunohistochemical analysis of YB-1 was performed using 163 surgically resected primary GC specimens. Results. YB-1 expression in cancer cells significantly differed with respect to Lauren type, JGCA classification, vascular invasion (VI), and microvessel density (MVD) of cancers (P = 0.018, P = 0.002, P < 0.001, and P < 0.001, respectively). No correlation was found between cancer-cell YB-1 expression and TNM stage or lymphatic invasion. However, YB-1 expression in vascular endothelial cells significantly correlated with N stage, M stage, TNM stage, and MVD of cancers (P < 0.001, P = 0.013, P < 0.001, and P < 0.001, respectively). Notably, cases with YB-1 expression in cancer vasculature also demonstrated YB-1 expression in cancer cells (P = 0.040). Conclusions. YB-1 may promote GC development through its function in both cancer cells and cancer vascular cells, and thus represent a potential biomarker in this disease (AU)

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Y-box binding protein 1 expression in gastric cancer subtypes and association with cancer neovasculature.

PURPOSE: Y-box binding protein 1 (YB-1) expression in cancer cells is closely associated with malignant progression and poor prognosis in various cancers. Recently, we demonstrated that YB-1 expression in cancer cells is an immunomarker for patient prognosis and liver metastasis of gastric cancer (GC), and identified YB-1 as an excellent biomarker of angiogenic and proliferating endothelial cells in cancers. We further explored the expression patterns of YB-1 in gastric vasculature and the relationship with the clinical pathologic characteristics, as well as YB-1 phenotype in cancer cells. METHODS/PATIENTS: Immunohistochemical analysis of YB-1 was performed using 163 surgically resected primary GC specimens. RESULTS: YB-1 expression in cancer cells significantly differed with respect to Lauren type, JGCA classification, vascular invasion (VI), and microvessel density (MVD) of cancers (P = 0.018, P = 0.002, P < 0.001, and P < 0.001, respectively). No correlation was found between cancer-cell YB-1 expression and TNM stage or lymphatic invasion. However, YB-1 expression in vascular endothelial cells significantly correlated with N stage, M stage, TNM stage, and MVD of cancers (P < 0.001, P = 0.013, P < 0.001, and P < 0.001, respectively). Notably, cases with YB-1 expression in cancer vasculature also demonstrated YB-1 expression in cancer cells (P = 0.040). CONCLUSIONS: YB-1 may promote GC development through its function in both cancer cells and cancer vascular cells, and thus represent a potential biomarker in this disease.

Two γ-ray bursts from dusty regions with little molecular gas.

Long-duration γ-ray bursts are associated with the explosions of massive stars and are accordingly expected to reside in star-forming regions with molecular gas (the fuel for star formation). Previous searches for carbon monoxide (CO), a tracer of molecular gas, in burst host galaxies did not detect any emission. Molecules have been detected as absorption in the spectra of γ-ray burst afterglows, and the molecular gas is similar to the translucent or diffuse molecular clouds of the Milky Way. Absorption lines probe the interstellar medium only along the line of sight, so it is not clear whether the molecular gas represents the general properties of the regions where the bursts occur. Here we report spatially resolved observations of CO line emission and millimetre-wavelength continuum emission in two galaxies hosting γ-ray bursts. The bursts happened in regions rich in dust, but not particularly rich in molecular gas. The ratio of molecular gas to dust (<9-14) is significantly lower than in star-forming regions of the Milky Way and nearby star-forming galaxies, suggesting that much of the dense gas where stars form has been dissipated by other massive stars.

Therapeutic window of lamotrigine for mood disorders: a naturalistic retrospective study.

INTRODUCTION: Lamotrigine is widely used for mood disorders including bipolar disorder and major depression, but its therapeutic levels have yet to be determined. This study was conducted to investigate the hypothesis that lamotrigine may have a therapeutic window for mood disorders. METHODS: 25 patients with mood disorders received lamotrigine for more than one year during which time plasma lamotrigine levels were measured at least once. Their mental state was retrospectively and regularly but blindly assessed using the Clinical Global Impression-Severity (CGI-S) scale. In order to investigate our hypothesis, we depicted the relationship between the last lamotrigine levels and the last CGI scores in 25 patients. If any, the potential therapeutic window was further investigated. RESULTS: The relationship between the last lamotrigine levels and the last CGI scores in the 25 patients indicated the presence of a therapeutic window of lamotrigine from 5 to 11 µg/mL. The repeated measures of ANOVA reached a significant tendency of the effects of lamotrigine levels within 5-11 µg/mL on better CGI-S scores, and the CGI-S scores at the last observation of the 15 patients whose lamotrigine levels were within 5-11 µg/mL were significantly better than those of 10 patients whose lamotrigine levels were not within 5-11 µg/mL. CONCLUSION: These findings suggest that lamotrigine may have a therapeutic window for patients with mood disorder from 5 to 11 µg/mL.

The combination of strong expression of ZNF143 and high MIB-1 labelling index independently predicts shorter disease-specific survival in lung adenocarcinoma.

BACKGROUND: The transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-related genes. The ZNF143 would show high expression of multiple solid tumours related closely to cancer cell growth, similar to the widely accepted Ki67 (MIB-1) protein, but the underlying mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143 expression with clinicopathological features and prognoses of patients with lung adenocarcinoma. METHODS: Expressions of ZNF143 and MIB-1 were immunohistochemically analysed in 183 paraffin-embedded tumour samples of patients with lung adenocarcinoma. The ZNF143 expression was considered to be strong when >30% of the cancer cells demonstrated positive staining. RESULTS: Strong ZNF143+ expression showed a significantly close relationship to pathologically moderate to poor differentiation and highly invasive characteristics. The ZNF143 positivity potentially induced cell growth of lung adenocarcinoma, correlated significantly with high MIB-1 labelling index (⩾10%). Univariate and multivariate analyses demonstrated that both strong ZNF143+ and the high MIB-1 index group have only and significantly worse survival rates. CONCLUSIONS: The combination of strong ZNF143 expression and high MIB-1 index potentially predicts high proliferating activity and poor prognosis in patients with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.

Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas.

BACKGROUND: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). METHODS: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. RESULTS: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low ß-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. CONCLUSION: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.

Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis.

High incidences of human herpesvirus (HHV)-6 encephalitis have recently been reported from several Japanese SCT centers. To evaluate the effect of low-dose foscarnet (PFA) in preventing HHV-6 infection among recipients of unrelated BM or cord blood (CB), we examined consecutive cohorts without prophylaxis against HHV-6 (cohort 1, n=51) and with PFA prophylaxis (cohort 2, PFA 50 mg/kg/day for 10 days after engraftment, n=67). Plasma real-time PCR assay was performed weekly. High-level reactivation defined as HHV-6 DNA > or =10(4) copies/mL by day 70 was the primary endpoint. No significant reduction of high-level reactivation was seen in cohort 2 (19.4%) compared with cohort 1 (33.8%, P=0.095). A trend was identified toward fewer high-level HHV-6 reactivations in cohort 2 among recipients of unrelated BM (P=0.067), but no difference in incidence was observed among CB recipients (P=0.75). Breakthrough HHV-6 encephalitis occurred following PFA prophylaxis in three patients, and incidence of HHV-6 encephalitis did not differ between cohort 1 (9.9%) and cohort 2 (4.5%, P=0.24). In conclusion, 50 mg/kg/day of PFA does not effectively suppress HHV-6 reactivation and cannot prevent all cases of HHV-6 encephalitis. To effectively prevent HHV-6 encephalitis, alternative approaches based on the pathogenesis of HHV-6 encephalitis will probably be required.

Recombinant high molecular weight-glutenin subunit-specific IgE detection is useful in identifying wheat-dependent exercise-induced anaphylaxis complementary to recombinant omega-5 gliadin-specific IgE test.

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a special form of food allergy typically induced by exercise after ingestion of wheat products. We identified wheat omega-5 gliadin and high molecular weight-glutenin subunit (HMW-glutenin) as major allergens for WDEIA and clarified that simultaneous detection of serum IgE binding to synthetic epitope peptides of these allergens identifies more than 90% of WDEIA patients. However, the short synthetic peptides are not suitable for CAP-fluorescent enzyme-immunoassay (CAP-FEIA), which is widely utilized for detecting allergen-specific IgE. OBJECTIVE: In this study, we constructed a CAP-FEIA with recombinant HMW-glutenin, and evaluated its usefulness in identifying the patients with WDEIA. METHODS: Recombinant HMW-glutenin was expressed as histidine-tag protein in E. coli and purified by histidine-tag affinity column. Wheat, gluten, recombinant omega-5 gliadin, epitope peptide of HMW-glutenin, native and recombinant HMW-glutenin specific IgE in the sera from 48 patients with WDEIA, 16 patients with atopic dermatitis (AD) who had no immediate allergic reaction after wheat ingestion and 12 healthy controls were determined by using CAP-FEIA method. RESULTS: In 16 AD patients without wheat allergy 12 of them (75%) had positive results for native HMW-glutenin test in contrast to epitope peptide of HMW-glutenin (12.5%) and recombinant HMW-glutenin test (12.5%). These results indicate the native HMW-glutenin test has low specificity. Sensitivity and specificity of the IgE test with recombinant HMW-glutenin were 16.7% and 92.9%. These are well compatible with results obtained by using epitope peptide of HMW-glutenin. However, sensitivity and specificity reached to 93.8% and 92.9%, when the test was combined to the test with recombinant omega-5 gliadin. CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrated that recombinant HMW-glutenin is best for CAP-FEIA system in point of stability and specificity and confirmed that detection of specific IgE against recombinant HMW-glutenin is useful for diagnosis of WDEIA when combined with the CAP-FEIA (recombinant omega-5 gliadin) test.

Prognostic significance of BAF57 expression in patients with endometrial carcinoma.

This study was conducted to elucidate the prognostic significance of BAF57 in patients with endometrial carcinoma. We investigated the relationship between the immunohistochemical expression of BAF57 and various clinicopathological variables in 111 endometrial carcinomas. Both univariate and multivariate regression analyses were performed. The correlations between the BAF57 expression and the other variables including estrogen receptor (ER) and p53 were examined. The high nuclear BAF57 expression was detected in 42 (37.8%) endometrial carcinomas, and 69 (62.2%) endometrial carcinomas were defined as having low nuclear BAF57 expression. The BAF57 expression was significantly associated with the surgical stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion (LVSI) and lymph node metastasis. The 10-year overall survival rates of patients with low and high BAF57 expression were 96.9% and 58.2%, respectively (p<0.001). A multivariate analysis identified BAF57 expression as an independent prognostic factor. The BAF57 expression was significantly correlated with p53 expression (r=0.312, P=0.001), but was not correlated with ER expression (r= -0.141, P=0.14). The high BAF57 expression is an independent marker of poor prognosis of the patients in endometrial carcinomas. The inhibition of BAF57 activity may be one of the candidates for endometrial cancer therapy, especially therapy for aggressive tumors showing overexpression of p53.

Overexpression of GalNAc-transferase GalNAc-T3 promotes pancreatic cancer cell growth.

O-linked glycans of secreted and membrane-bound proteins have an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues and suppression of GalNAc-T3 significantly attenuates the growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine the nucleotide-binding protein, α-transducing activity polypeptide-1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1 and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers.

Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

BACKGROUND: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. METHODS: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. RESULTS: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). CONCLUSION: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

Correlations of HHV-6 viral load and plasma IL-6 concentration with HHV-6 encephalitis in allogeneic stem cell transplant recipients.

This study investigated factors associated with the development of human herpesvirus (HHV)-6 encephalitis. Among 111 enrolled subjects, 12 patients developed central nervous system (CNS) dysfunction. CNS dysfunction in four patients was found to have no association with HHV-6. The remaining eight patients displayed HHV-6 encephalitis (n=3), limbic encephalitis (HHV-6 DNA in cerebrospinal fluid was not examined; n=3) or CNS dysfunction because of an unidentified cause (n=2). Real-time PCR showed CNS dysfunction in the latter eight patients, which developed concomitant with the appearance of high plasma levels of HHV-6 DNA (> or =10(4) copies/ml). Overall, eight of the 24 patients with high-level HHV-6 DNA developed CNS dysfunction, whereas no patients developed CNS dysfunction potentially associated with HHV-6 infection if peak HHV-6 DNA was <10(4) copies/ml. We next analyzed plasma concentrations of IL-6, IL-10 and tumor necrosis factor-alpha among patients who displayed high-level plasma HHV-6 DNA and found elevated IL-6 concentrations preceding HHV-6 infection in patients who developed CNS dysfunction. (Mean+/-s.d.: 865.7+/-1036.3 pg/ml in patients with CNS dysfunction; 56.5+/-192.9 pg/ml in others; P=0.01). These results suggest that high-level HHV-6 load is necessary for the development of HHV-6 encephalitis, and systemic inflammatory conditions before HHV-6 infection form the preparatory conditions for progression to encephalopathy.