Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?

We found that congenital uterine anomalies have a negative impact on reproductive outcome in recurrent-miscarriage couples, being associated with further miscarriage with a normal embryonic karyotype. There has been no study comparing live birth rates between patients with and without surgery. We conducted a prospective study to prove that surgery for a bicornuate or septate uterus might improve the live birth rate. A total of 170 patients with congenital uterine anomalies suffering two or more miscarriages were examined. The live birth rate after ascertainment of anomalies, cumulative live birth rate and infertility rate, were compared between patients with and without surgery. In patients with a septate uterus, the live birth rate (81.3%) at the first pregnancy after ascertainment of anomalies with surgery tended to be higher than that (61.5%) in those without surgery. The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for having a baby, but tended to decrease the preterm birth rate and the low birth weight. The possibility that surgery has benefits for having a baby in patients with a septate uterus suffering recurrent miscarriage could not be excluded.

MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer.

BACKGROUND: FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal squamous cell carcinoma (ESCC). METHODS: FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells. RESULTS: The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression. CONCLUSION: The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.

BMP-2 induces ATF4 phosphorylation in chondrocytes through a COX-2/PGE2 dependent signaling pathway.

OBJECTIVE: Bone morphogenic protein (BMP)-2 is approved for fracture non-union and spine fusion. We aimed to further dissect its downstream signaling events in chondrocytes with the ultimate goal to develop novel therapeutics that can mimic BMP-2 effect but have less complications. METHODS: BMP-2 effect on cyclooxygenase (COX)-2 expression was examined using Real time quantitative PCR (RT-PCR) and Western blot analysis. Genetic approach was used to identify the signaling pathway mediating the BMP-2 effect. Similarly, the pathway transducing the PGE2 effect on ATF4 was investigated. Immunoprecipitation (IP) was performed to assess the complex formation after PGE2 binding. RESULTS: BMP-2 increased COX-2 expression in primary mouse costosternal chondrocytes (PMCSC). The results from the C9 Tet-off system demonstrated that endogenous BMP-2 also upregulated COX-2 expression. Genetic approaches using PMCSC from ALK2(fx/fx), ALK3(fx/fx), ALK6(-/-), and Smad1(fx/fx) mice established that BMP-2 regulated COX-2 through activation of ALK3-Smad1 signaling. PGE-2 EIA showed that BMP-2 increased PGE2 production in PMCSC. ATF4 is a transcription factor that regulates bone formation. While PGE2 did not have significant effect on ATF4 expression, it induced ATF4 phosphorylation. In addition to stimulating COX-2 expression, BMP-2 also induced phosphorylation of ATF4. Using COX-2 deficient chondrocytes, we demonstrated that the BMP-2 effect on ATF4 was COX-2-dependent. Tibial fracture samples from COX-2(-/-) mice showed reduced phospho-ATF4 immunoreactivity compared to wild type (WT) ones. PGE2 mediated ATF4 phosphorylation involved signaling primarily through the EP2 and EP4 receptors and PGE2 induced an EP4-ERK1/2-RSK2 complex formation. CONCLUSIONS: BMP-2 regulates COX-2 expression through ALK3-Smad1 signaling, and PGE2 induces ATF4 phosphorylation via EP4-ERK1/2-RSK2 axis.

Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in blood and can serve as useful biomarkers for cancer. METHODS: We performed an miRNA array using serum samples obtained from oesophageal squamous cell carcinoma (ESCC) patients or healthy controls. MiR-1246 was the most markedly elevated in ESCC patients. Therefore, miR-1246 was selected as a candidate for further analysis. The serum miR-1246 level in 46 healthy controls and 101 ESCC patients was evaluated and compared among various clinicopathological characteristics. MiR-1246 expressions in tissue, exosomal, and cellular samples were also examined. RESULTS: Serum miR-1246 alone yielded an receiver-operating characteristic curve area of 0.754, with 71.3% sensitivity and 73.9% specificity for distinguishing ESCC patients from healthy controls. Serum miR-1246 was significantly correlated with the TNM stage and showed to be the strongest independent risk factor for poor survival (HR, 4.032; P=0.017). Unlike the tendency shown in previous reports, miR-1246 was not upregulated in ESCC tissue samples. Furthermore, exosomal miR-1246 did not reflect the abundance in the cell of origin. CONCLUSION: These data support our contention that serum miR-1246 has strong potential as a novel diagnostic and prognostic biomarker in ESCC, and its releasing mechanism is selective and independent of tissue miRNA abundance.

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer.

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.

Psychological adjustment and psychosocial stress among Japanese couples with a history of recurrent pregnancy loss.

BACKGROUND: Little is known about the effects of recurrent pregnancy loss (RPL) on the psychological adjustment of couples. The aim of this study was to elucidate psychological adjustment and RPL-associated psychosocial stress affecting Japanese couples with a history of RPL, focusing on gender differences and quality of the marital relationship. METHODS: The study included 76 RPL couples who visited the outpatient clinic of a tertiary hospital. They completed self-administered questionnaires that assessed RPL-associated stress, quality of their marital relationship (Quality Marriage Index, QMI), depression (Beck Depression Index) and anxiety (State-Trait Anxiety Inventory). RESULTS: Women showed significantly higher levels of depression, anxiety and RPL-associated personal and social stress compared with men. Although there were no differences in QMI scores and RPL-associated marital stress between men and women, women with a low perception of marital relationship quality (low QMI) had significantly higher levels of depression and anxiety compared with women with a moderate or high QMI. In contrast, depression and anxiety scores did not differ according to the quality of the marital relationship among men. Of 76 couples, 26 men (34%) and 45 women (59%) who had considered professional mental health consultations regarding their RPL status but had not yet initiated the process were more depressed and anxious than 48 men and 24 women, respectively, who had never considered such consultation. CONCLUSIONS: Women were significantly more distressed than men. Poor quality of the marital relationship was significantly associated with impaired psychological adjustment among women, but not among men. These gender discrepancies may foster a mutual worsening of psychological adjustment and marital relationships in RPL couples. The need to seek help not only in women but also in a substantial portion of men suggests the importance of couple-based psychological care in the management of RPL.

Arginine 485 of human serum albumin interacts with the benzophenone moiety of ketoprofen in the binding pocket of subdomain III A and III B.

Arylpropionic acid nonsteroidal anti-inflammatory drusg (NSAIDs) primarily bind to subdomain III A (site II) of human serum albumin (HSA). Ketoprofen (KP), an arylpropionic acid that contains a photoreactive benzophenone moiety, was used to photolabel the binding region of site II. LC/Q-TOF mass spectrometry determination revealed that R485 was the amino acid residue that formed covalent adduct with the benzophenone moiety of KP. Point mutation of arginine 485 to alanine showed a slight decrease in the overall binding percentage of KP when compared to that of native HSA. The induced circular dichroism spectral data of KP with both R485A and native albumin confirmed the photolabeling findings. Interestingly, an increase in the extent of [14C]KP covalent adduct formation with the 11.6 kDa peptide derived from subdomain IIB-IIIA was observed for R485A. In contrast, mutation of arginine 410 caused a significant reduction of binding percentage, confirming the importance of this residue in high affinity binding of arylpropionic acid derivatives. This may indicate that while KP's carboxylate interacts electrostatically with arginine 410, the benzophenone moiety may have swung away from helix 6 in the absence of arginine 485. In this study, photolabeling of native and mutants albumins, R485A and R410C with [14C]KP confirmed that R485 involved in the non-electrostatic interaction with the benzophenone moiety of KP, but not vital to hold KP in the binding pocket of subdomain IIIA.

Establishment of recombinant hybrid-IgG/IgA immunoglobulin specific for Shiga toxin.

Shiga toxin 1 produced by enterohaemorrhagic Escherichia coli is an AB(5) toxin that is involved in the life-threatening haemolytic-uraemic syndrome. The B subunits (Stx1B) are cell-binding subunits. We previously established mouse hybridoma cell line producing IgA and IgG monoclonal antibodies (mAbs) against Stx1B. Here, we cloned cDNAs encoding each of the heavy, light and joining (J) chains from the hybridoma cell lines by means of the 5' rapid amplification of cDNA ends (RACE) PCR method. Upon assignment of the variable regions of the heavy and light chains to known germline sequences, we found substantial somatic hypermutation in the complementarity-determining regions in both the IgA and IgG mAbs. We also established a hybrid-IgG/IgA heavy chain having variable regions of the IgG mAb by means of recombinant PCR methods. Upon transient expression of the hybrid-IgG/IgA heavy, IgG-associated light and J chains in COS-1 cells, the translated dimeric hybrid-IgG/IgA bound to immobilized Stx1B, as revealed on ELISA. The production of dimeric hybrid-IgG/IgA was revealed on immunoblot analysis. The dimeric hybrid-IgG/IgA inhibited the binding of digoxigenin-conjugated Stx1B to natural ligands (CD77) displayed on Burkitt's lymphoma cell line Ramos. These results indicate that the replacement of variable regions resulted in the production of more useful recombinant dimeric IgA against Stx1B.

Search for a new gauge boson in electron-nucleus fixed-target scattering by the APEX experiment.

We present a search at the Jefferson Laboratory for new forces mediated by sub-GeV vector bosons with weak coupling α' to electrons. Such a particle A' can be produced in electron-nucleus fixed-target scattering and then decay to an e + e- pair, producing a narrow resonance in the QED trident spectrum. Using APEX test run data, we searched in the mass range 175-250 MeV, found no evidence for an A'→ e+ e- reaction, and set an upper limit of α'/α ~/= 10(-6). Our findings demonstrate that fixed-target searches can explore a new, wide, and important range of masses and couplings for sub-GeV forces.

Disopyramide-induced hypoglycemia in a non-diabetic hemodialysis patient: a case report and review of the literature.

Disopyramide, an antiarrhythmic drug, has been reported to cause hypoglycemia; however, its mechanism of action remains unclear. Pre-existing factors that increase the concentration of the drug in the blood increase the risk of hypoglycemia. Furthermore, other factors can also increase the risk of hypoglycemia even when disopyramide levels are in the therapeutic range. It has been proposed that disopyramide-induced hypoglycemia is caused by stimulation of insulin secretion due to the inhibition of the pancreatic beta-cell ATP-sensitive K+ channels. We report a case of severe disopyramide-induced hypoglycemia in a nondiabetic 72-year-old woman on hemodialysis. Concentrations of counter-regulatory hormones, serum insulin, and C-peptide were measured. From these data, it appears that disopyramide-induced hypoglycemia results from sustained endogenous insulin secretion, with a concomitant inadequate counter-regulatory response. Although hypoglycemia occurs infrequently in patients treated with disopyramide, this adverse effect is clinically important and potentially life-threatening. Evidence suggests that disopyramide-induced hypoglycemia results from endogenous insulin secretion and can occur in patients with therapeutic blood concentrations of the drug. Patients at risk include those with renal impairment, advanced age, and malnutrition, and blood glucose levels should be monitored carefully in such patients.

Influence of common cardiac drugs on gastroesophageal reflux disease: multicenter questionnaire survey.

BACKGROUND: Although gastroesophageal reflux disease (GERD) causes noncardiac chest pain mimicking angina pectoris, systemic studies surveying the effects of common cardiac drugs on symptomatic GERD are rare. METHODS: To investigate the drugrelated GERD, this multicenter trial enrolled 201 consecutive cardiac outpatients (69.7 ± 10.5 y) after obtaining written informed consent. They were assessed using the Frequency Scale for Symptoms of GERD (F-scale) to screen for GERD with a cut-off value of 8.0. Clinical background was obtained from medical records. Gastric medicine was empirically administered at the discretion of the attending physician. F-scale score and incidence of GERD were analyzed individually in relation to background and prescription. RESULTS: The average F-scale score did not correlate with gender, age or underlying diseases. F-scale score was elevated significantly (p = 0.006) by administration of calcium channel blockers to the patients treated with gastric medicine, suggesting that calcium channel blockers exacerbate the possibly preexisting GERD. Incidence of GERD within 2 months after starting warfarin tended to be greater than that at other durations (p = 0.087). Patients showing a high score (≥ 8.0) suggestive of GERD showed a correlation with the combined administration of calcium channel blockers (OR = 3.19; 95% CI of 1.01 - 10.11; p = 0.049) and warfarin (OR = 3.05; 95% CI of 1.00 - 9.27; p = 0.049) in the best logistic model. CONCLUSION: Although larger cohort is required, this survey demonstrates that the combination of calcium channel blockers and warfarin is an independent risk factor for GERD.

Beta 1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients.

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin-mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.

Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.

BACKGROUND: We previously reported that Trastuzumab- and Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer patients was impaired in comparison with that in healthy donors because of NK-cell dysfunction. In this study, we evaluated whether IL-21 could improve the impairment of ADCC in patients with oesophageal squamous cell carcinoma (ESCC), as IL-21 was reported to have the ability to activate NK cells. METHODS: We examined Trastuzumab- and Cetuximab-mediated ADCC of peripheral blood mononuclear cells (PBMCs) or of enriched NK cells derived from ESCC patients (n=20) and healthy donors (n=16) in the presence of IL-21. We further analysed ADCC-related molecules (perforin, granzyme-B, and CD247) on NK cells in response to IL-21. RESULTS: Trastuzumab- and Cetuximab-mediated ADCC of PBMCs or of enriched NK cells was enhanced by the addition of IL-21 in a dose-dependent manner and the levels of ADCC enhanced by IL-21 in patients were high enough in comparison with those in healthy donors, paralleling the upregulation of CD247 on NK cells. CONCLUSION: IL-21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules.

Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.

BACKGROUND: As HER2 is expressed in 30% of oesophageal squamous cell carcinomas (ESCCs), T-cell-based immunotherapy and monoclonal antibodies targeted against HER2 are attractive, novel approaches for ESCCs. However, it was shown that there is an inverse correlation between HER2 and MHC class I expression on tumours. Thus, the correlation between HER2 and MHC class I expressions on ESCC was evaluated. METHODS: Expressions of MHC class I and HER2 in ESCC tissues (n=80) and cell lines were assessed by immunohistochemistry, fluorescence in situ hybridisation (FISH), and flow cytometry. We investigated whether HER2 downregulation with small interfering RNA (siRNA) in ESCC cell lines could upregulate the expression of MHC class I and the antigen presentation machinery components, and could increase their sensitivity for tumour antigen-specific CTLs. RESULTS: There was an inverse correlation between HER2 and MHC class I expressions in both tumour tissues and cell lines. Downregulation of HER2 with siRNA resulted in the upregulation of MHC class I expression, leading to increased CTL recognition by tumour antigen-specific CTLs. CONCLUSION: HER2-overexpressing ESCC tumour cells showed a reduced sensitivity for CTLs through the downregulation of MHC class I.

OCT4 expression in human uterine myometrial stem/progenitor cells.

BACKGROUND: The transcription factor, octamer-binding transcription factor 4 (OCT4)/POU5F1, is expressed in embryonic stem cells, germ cells and some types of adult stem cells. Human OCT4 encodes two isoforms, OCT4A and OCT4B. While OCT4A plays a crucial role in the maintenance of stem cell properties, including pluripotency, whereas OCT4B does not. We previously reported that human myometrium contains side population cells (myoSP) with a Hoechst 33 342 low-fluorescent profile. These cells exhibit phenotypic and functional characteristics of myometrial stem cells. The objective of this study was to investigate the comparative expression of OCT4 in the stem/progenitor cell population of the human myometrium. METHODS: Human myometrial tissue samples were collected from 18 consenting patients who underwent hysterectomy because of benign gynecological diseases. The resultant isolated or cultured myometrial cells and isolated myoSP were subjected to semi-quantitative and real-time RT-PCR analyses, immunoblot analyses and immunohistochemistry. RESULTS: RT-PCR and immunoblot analyses revealed that OCT4 mRNA and OCT4 protein were detectable in some (but not all) myometrial samples. Immunohistochemistry showed that OCT4 protein was confined to the nuclei of relatively few cells in myometrial tissues expressing OCT4 mRNA. OCT4 and OCT4A transcripts, but not those of OCT4B, were more abundant in myoSP than in non-myoSP, as determined by real-time and semi-quantitative RT-PCR analyses. CONCLUSIONS: Relatively few myometrial cells express OCT4 protein. OCT4 mRNA, in particular OCT4A mRNA, is up-regulated in myoSP that have been reported to exhibit stem cell-like properties. Taken together, the present results indicate that the myoSP population is enriched in OCT4 mRNA.

Effect of annealing in hydrogen atmosphere on carbon nanocap formation in surface decomposition of 6H-SiC(000-1).

We investigated the effect of annealing in a hydrogen atmosphere on carbon nanocap formation during decomposition of a 6H-SiC(000-1) surface. It was determined that native oxides were reduced to below the detection limit of X-ray photoelectron spectroscopy after 30 min of annealing at 1200 degrees C in a hydrogen atomosphere at 10(-3) Pa. In addition, we found that the homogeneity of carbon nanocap size was improved on the SiC surface, compared with a sample annealed in ultra-high vacuum. This technique will be useful in the fabrication of homogeneous carbon nanotube layers by surface decomposition of SiC.

Low-temperature synthesis of single-walled carbon nanotubes by alcohol gas source growth in high vacuum.

Carbon nanotube (CNT) growth was carried out on SiO2/Si substrates with a Co catalyst using an alcohol gas source method in an ultra-high vacuum chamber. The resulting CNTs were characterized by scanning electron microscopy (SEM), Raman spectroscopy and transmission electron microscopy (TEM). Reducing the ethanol pressure decreased the optimum growth temperature for maximum yield, enabling single-walled carbon nanotube (SWNT) growth at 400 degrees C. By employing an Al2Ox buffer layer, SWNT yield increased several times, even at 400 degrees C. Under TEM observation, the Co particle size on the Al2Ox layers did not show a significant dependence on the growth temperature between 400 and 700 degrees C. Raman and TEM results confirmed activation of Co particles with larger diameter (>1 nm) by the Al2Ox buffer layer.

Blood pressure-lowering and antiproteinuric effect of switching from high-dose angiotensin receptor blockers to normal-dose telmisartan and low-dose hydrochlorothiazide in hypertensive patients with chronic kidney disease.

OBJECTIVES: We evaluated the changes in the blood pressure and urinary protein excretion in poorly controlled hypertensive and proteinuric patients with mild to moderate chronic kidney disease (CKD) after switching from the high-dose angiotensin receptor blockers (ARBs) to a combination of normal-dose telmisartan (40 mg) and low-dose hydrochlorothiazide (HCTZ; 12.5 mg). METHODS: 60 adults with Stages 2 - 3 CKD who had been receiving high-dose ARBs and had not achieved their target blood pressure of 130/80 mmHg were switched to a combination of telmisartan (40 mg) and HCTZ (12.5 mg) once daily for a 12-week study period. We measured the blood pressure, pulse rate, urinary protein excretion, and total monthly drug costs before and after the switch. RESULTS: The mean systolic blood pressure dropped from 153 to 133 mm Hg and the mean diastolic blood pressure, from 89 to 78 mmHg (p < 0.0001, for both). Further, the mean blood pressure decreased (p < 0.0001), without any significant change in the pulse rate. Urinary protein excretion adjusted for urinary creatinine was reduced from 3,749 to 2,474 mg/g creatinine (p < 0.0001). No significant change was detected in the estimated glomerular filtration rate and serum creatinine level. With the switching from high-dose ARBs to the combination of normal-dose telmisartan and low-dose HCTZ treatment, the blood pressure decreased in all the subjects, and 36% of all the subjects achieved optimal blood pressure levels. No adverse metabolic effects were noted even among the diabetic patients. The monthly drug costs were significantly reduced after the switch (13,614 +/- 6,108 vs. 9,936 +/- 5,571 yen/month, p < 0.0001). CONCLUSIONS: We concluded that the telmisartan and HCTZ combination may be more efficacious than monotherapy of the high-dose ARBs in reducing blood pressure and urinary protein excretion in hypertensive patients with CKD. Further investigation would be required to assess whether the combination of high-dose ARBs and low-dose HCTZ has a greater antiproteinuric effect than the combination of normal-dose telmisartan (40 mg) and low-dose HCTZ (12.5 mg).

NK cell dysfunction with down-regulated CD16 and up-regulated CD56 molecules in patients with esophageal squamous cell carcinoma.

NK cells can be divided into two subsets, CD56(dim) and CD56(bright) NK cells, based on their expression of CD56 and CD16. In the present study, we analyzed NK cell dysfunction in patients with esophageal squamous cell carcinoma (ESCC), with a particular focus on the expression of CD16 and CD56 molecules. Expression of CD16 and CD56, and the distribution of CD56(dim) or CD56(bright) NK cells gated on CD56(+)CD3(-) NK cells were compared between ESCC patients (n= 40) and healthy donors (n= 38). Purified NK cells were evaluated for Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against epidermal growth factor receptor (EGFR)-expressing ESCC cell lines. Although there were no significant differences in the distribution of CD56(dim) and CD56(bright) NK cells between ESCC patients and healthy donors, down-regulated CD16 and up-regulated CD56 were significantly observed on NK cells of ESCC patients, paralleling the impairment of Cetuximab-mediated ADCC, in comparison with healthy donors. After patients received curative resections of ESCC, the down-regulated CD16 and up-regulated CD56 were significantly restored to the levels of healthy donors. Moreover, TGF-beta1 partially contributed to down-regulation of CD16 on NK cells. Down-regulated CD16 and up-regulated CD56 molecules on NK cells were observed in ESCC patients, resulting in NK cell dysfunction.