Factors associated with a positive willingness to practise oral health care in the future amongst oral healthcare and nursing students.

OBJECTIVES: The purpose of this study was to identify the weak points in the knowledge and attitudes of first-year oral health care and nursing students towards oral health care and to identify the factors associated with their positive willingness to practise oral health care after becoming a health professional in order to develop oral healthcare curricula. MATERIALS AND METHODS: The subjects were 88 first-year dental students (DSs), 64 dental hygiene students (DHSs) and 119 nursing students (NSs) enrolled in schools in Japan, as of April 2017. A questionnaire was distributed to subjects in each school to assess their knowledge and attitudes towards oral health care. RESULTS: Less than half knew that oral health care was also provided in cancer hospitals, hospices, acute care hospitals, maternity wards and psychiatric wards. Only 46.2% knew that oral health care was effective in the prevention of aspiration pneumonia. The level of knowledge and attitudes in NSs regarding oral health care were likely to be lowest amongst the student groups. Only NSs' high interest towards oral health care was associated with their positive willingness to practise oral health care in the future although oral health students' high perceptions and interest regarding oral health care were associated with the willingness. CONCLUSION: This study showed oral healthcare and nursing students' weak points regarding their attitudes and knowledge of oral health care at early stages. Oral health academic staff and professionals should develop effective oral healthcare curricula for oral healthcare students and help nursing staff develop a collaborative nursing oral healthcare curriculum to motivate nursing students.

Effective wound bed preparation using maggot debridement therapy for patients with critical limb ischaemia.

OBJECTIVE: Patients with critical limb ischaemia (CLI) lack sufficient blood flow in to the limb, which leads to difficulties in the normal wound healing process. Therefore, maggot debridement therapy (MDT) has not generally been recommended for CLI patients. We evaluated the effectiveness of wound bed preparation by MDT in CLI patients who had undergone mid-foot amputation. METHODS: Patients who underwent mid-foot amputation after angioplasty between April 2014 and October 2016 were retrospectively investigated by classifying them into an MDT group or a conventional treatment group. The primary outcome was defined as achievement of wound healing. Secondary outcomes were the proportions of amputation-free survival (AFS) and successful ambulatory improvement. Propensity scores were used to evaluate treatment outcomes based on five factors: ankle-brachial index, skin perfusion pressure of the foot, nutritional status, experience with dialysis and age. RESULTS: A total of 39 patients (39 legs) were included, seven within the MDT group and 32 in the conventional treatment group. Clinical backgrounds of the two groups showed no significant differences except for higher albumin levels for the MDT group (3.5±0.4g/dl; p=0.014). The wound healing proportion was significantly higher in the MDT group (86%) than in the control group (38%) (p=0.035). At 6 months after amputation, no significant differences were found between the two groups for AFS (71% versus 47%; p=0.41) or ambulatory capability (43% versus 28%; p=0.65). This result was also similar to the propensity score adjustment analysis. CONCLUSIONS: The efficacy of MDT with favourable wound bed preparation was shown in our CLI patients based on effective debridement and granulation formation by maggots, avoiding the loss of their heels. Wound-healing rates after MDT were higher for patients than for those receiving conventional treatment. MDT is considered a valid adjuvant treatment strategy for patients with CLI after revascularisation treatment is conducted. More favourable wound bed preparation and successful graft take were achieved in the MDT group, suggesting the effectiveness of MDT for wound healing in CLI patients.

REPEATED INTRANODAL LYMPHANGIOGRAPHY FOR THE TREATMENT OF LYMPHATIC LEAKAGE.

Treatment of patients with chylous or non-chylous lymphatic leakage can be difficult. An approach using therapeutic lymphangiography can reduce the lymphatic leakage, but it seldom stops the leakage immediately and subsequent conservative treatment is necessary. We report three cases in which intranodal lymphangiography was performed multiple times to inhibit lymphatic leakage. In each case, the lymph node was punctured under ultrasound guidance using a 23-gauge needle and lipiodol was injected manually at a rate of 1 ml/3 min. The procedure was repeated twice in two cases of gastrointestinal carcinoma and four times in one case of lymphoma. In all three cases, the postoperative lymphatic leakage stopped after the repeated intranodal lymphangiography.

Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.

BACKGROUND: Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. METHODS: We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. RESULTS: The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. CONCLUSIONS: Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.

Down-regulated expression of monocyte/macrophage major histocompatibility complex receptors in human and mouse monocytes by expression of their ligands.

Mouse monocyte/macrophage major histocompatibility complex (MHC) receptor 1 (MMR1; or MMR2) specific for H-2D(d) (or H-2K(d) ) molecules is expressed on monocytes from non-H-2D(d) (or non-H-2K(d) ), but not those from H-2D(d) (or H-2K(d) ), inbred mice. The MMR1 and/or MMR2 is essential for the rejection of H-2D(d) - and/or H-2K(d) -transgenic mouse skin onto C57BL/6 (H-2D(b) K(b) ) mice. Recently, we found that human leucocyte antigen (HLA)-B44 was the sole ligand of human MMR1 using microbeads that had been conjugated with 80 types of HLA class I molecules covering 94·2% (or 99·4%) and 92·4% (or 96·2%) of HLA-A and B molecules of Native Americans (or Japanese), respectively. In the present study, we also explored the ligand specificity of human MMR2 using microbeads. Microbeads coated with HLA-A32, HLA-B13 or HLA-B62 antigens bound specifically to human embryonic kidney (HEK)293T or EL-4 cells expressing human MMR2 and to the solubilized MMR2-green fluorescent protein (GFP) fusion protein; and MMR2(+) monocytes from a volunteer bound HLA-B62 molecules with a Kd of 8·7 × 10(-9) M, implying a three times down-regulation of MMR2 expression by the ligand expression. H-2K(d) (or H-2D(d) ) transgene into C57BL/6 mice down-regulated not only MMR2 (or MMR1) but also MMR1 (or MMR2) expression, leading to further down-regulation of MMR expression. In fact, monocytes from two (i.e. MMR1(+) /MMR2(+) and MMR1(-) /MMR2(-) ) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMRs on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMRs on macrophages toward allografts in tissue.

A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.

Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy. Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR). Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells. There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry. Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401. OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection. OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells. OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods. OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples. These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.

Risk factors for major morbidity after liver resection for hepatocellular carcinoma.

BACKGROUND: Bile leakage, and organ and/or space surgical-site infection (SSI) are common causes of major morbidity after partial hepatectomy for hepatocellular carcinoma (HCC). The purpose of this study was to analyse risk factors for major morbidity and to explore strategies for its reduction after partial hepatectomy for HCC. METHODS: Risk factors for bile leakage and organ/space SSI were analysed in patients who underwent partial hepatectomy for HCC between 2001 and 2010. The causes, management and outcomes of intractable bile leakage requiring endoscopic therapy or percutaneous transhepatic biliary drainage were analysed. In addition, causative bacteria, outcomes and characteristics of organ/space SSI were investigated. Risk factors were identified using multivariable analysis. RESULTS: Some 359 patients were included in the analysis. The prevalence of bile leakage and organ/space SSI was 12·8 and 8·6 per cent respectively. Repeat hepatectomy and an operating time of at least 300 min were identified as independent risk factors for bile leakage. The main causes of intractable bile leakage were latent strictures of the biliary system caused by previous treatments for HCC and intraoperative injury of the hepatic duct during repeat hepatectomy. Independent risk factors for organ/space SSI were repeat hepatectomy and bile leakage. Methicillin-resistant Staphylococcus aureus was detected more frequently in organ/space SSI after repeat hepatectomy than after initial partial hepatectomy. CONCLUSION: Repeat hepatectomy and prolonged surgery were identified as risk factors for bile leakage after liver resection for HCC. Bile leakage and repeat hepatectomy increased the risk of organ/space SSI.

CO2 microbubble contrast enhancement in x-ray angiography.

AIM: To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement depicts blood vessels when used for x-ray examinations. MATERIALS AND METHODS: Microbubbles were generated by cavitation of physiological saline to which CO2 gas had been added using an ejector-type microbubble generator. The input pressure values for CO2 gas and physiological saline that produced a large quantity of CO2 microbubbles were obtained in a phantom. In an animal study, angiography was performed in three swine using three types of contrast: CO2 microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2 microbubble contrast enhancement, physiological saline, and CO2 gas were supplied at the input pressures calculated in the phantom experiment. Regions of interest were set in the abdominal aorta, external iliac arteries, and background. The difference in digital values between each artery and the background was calculated. RESULTS: The input pressures obtained in the phantom experiment were 0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological saline input volume being 8.1 ml/s. Three interventional radiologists all evaluated the depictions of all arteries as "present" in the CO2 microbubble contrast enhancement, conventional CO2 contrast enhancement, and iodinated contrast enhancement performed in three swine. Digital values for all vessels with microbubble CO2 contrast enhancement were higher than background values. CONCLUSIONS: In x-ray angiography, blood vessels can be depicted by CO2 microbubble contrast enhancement, in which a large quantity of CO2 microbubbles is generated within blood vessels.

A new peltogastrid rhizocephalan parasitising a hermit crab from the Japanese coast: a second species of Dipterosaccus Van Kampen & Boschma, 1925 (Crustacea: Cirripedia).

A new rhizocephalan species of the genus Dipterosaccus Van Kampen & Boschma, 1925, is described from the host hermit crab Calcinus vachoni Forest on the coasts of mainland Japan and the Ryukyu Archipelago. Dipterosaccus shiinoi n. sp. differs from the previously described species, D. indicus Van Kampen & Boschma, 1925, which is redescribed, principally in the morphology of the mantle aperture and the disposition of the receptacle ducts. The distribution ranges of the two species partly overlap and they are sympatric at the same reef site near Okinawa Island. Their differentiation as two distinct species was confirmed by partial sequences of the COI gene. The monophyly of Dipterosaccus is supported by high Bayes posterior possibility and bootstrap values.

Bayes estimators for phylogenetic reconstruction.

Tree reconstruction methods are often judged by their accuracy, measured by how close they get to the true tree. Yet, most reconstruction methods like maximum likelihood (ML) do not explicitly maximize this accuracy. To address this problem, we propose a Bayesian solution. Given tree samples, we propose finding the tree estimate that is closest on average to the samples. This "median" tree is known as the Bayes estimator (BE). The BE literally maximizes posterior expected accuracy, measured in terms of closeness (distance) to the true tree. We discuss a unified framework of BE trees, focusing especially on tree distances that are expressible as squared euclidean distances. Notable examples include Robinson-Foulds (RF) distance, quartet distance, and squared path difference. Using both simulated and real data, we show that BEs can be estimated in practice by hill-climbing. In our simulation, we find that BEs tend to be closer to the true tree, compared with ML and neighbor joining. In particular, the BE under squared path difference tends to perform well in terms of both path difference and RF distances.

Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma.

BACKGROUND: Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in OSCC. METHODS: We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery. RESULTS: The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P=0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic factors for OSCC patients. CONCLUSION: These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance.

Urgent endovascular treatment of thoraco-abdominal aneurysms using a sandwich technique and chimney grafts--a technical description.

INTRODUCTION: So far the only endovascular option to treat patients with thoraco abdominal aortic aneurysms is the deployment of branched grafts. We describe a technique consisting of the deployment of standard off-the- shelf grafts to treat urgent cases. MATERIAL AND METHODS: The sandwich technique consists of the deployment of ViaBahn chimney grafts in combination with standard thoracic and abdominal aortic stent grafts. The chimney grafts are deployed using a transbrachial and transaxillary access. These coaxial grafts are placed inside the thoracic tube graft. After deployment of the infrarenal bifurcated abdominal graft a bridging stent-a short tube graft is positioned inside the thoracic graft further stabilizing the chimney grafts. RESULTS: 5 patients with symptomatic thoraco abdominal aneurysms were treated. There was one Type I endoleak that resolved after 2 months. In all patients 3 stentgrafts had to be used When possible all visceral and renal branches were revascularized. A total number of 17 arteries were reconnected with covered branches. During follow up we lost one target vessel the right renal artery. CONCLUSION: The sandwich technique in combination with chimney grafts permits a total endovascular exclusion of thoraco abdominal aortic aneurysms. In all cases off-the shelf products and grafts could be used. The number of patients treated so far is still too small to draw further more robust conclusions with regard to long term performance and durability.

Total endovascular debranching of the aortic arch.

BACKGROUND: Significant morbidity and mortality are related to conventional aortic replacement surgery. Endovascular debranching techniques, fenestrated or branched endografts are time consuming and costly. OBJECTIVE: We alternatively propose to use endovascular approach with parallel grafts for debranching of aortic arch. METHODS: Under general anesthesia, 12 F sheaths were inserted in the femoral, axillary and common carotid arteries for vascular accesses. ViaBahn grafts 10 - 15 cm in length were placed into the aortic arch from right common carotid, left common carotid and left axillary arteries, until the tip of each graft reached into the ascending aorta. Through one femoral artery, the aortic stent -graft was positioned and delivered. Soon after, the parallel grafts were sequentially delivered. Self-spanding Wallstents(R) were used for parallel grafts reinforcement. Ballooning was routinely used for parallel grafts and rarely for aortic graft. RESULTS: This technique was used in 2 cases. The first one was a lady with 72 years old, with an aortic retrograde dissection from left subclavian artery and involving remaining arch branches. Through right common carotid artery a stent-graft was placed in the ascending aorta and through the left common carotid artery a ViaBahn was inserted parallel to the former. A thoracic endograft then covered all the aortic arch dissection extending into the ascending aorta close to the sinu -tubular junction. The second case was a 82 year old male patient with a 7 cm aortic arch aneurysm. Through both common carotid arteries ViaBahn grafts were introduced and positioned into the ascending aorta. Soon after, the deployment of the thoracic stent graft covered all parallel grafts of the aortic arch, excluding the aneurysm. Both cases did not have neurologic or cardiac complications and were discharged 10 days after the procedure. CONCLUSIONS: This technique may be a good minimal invasive off-the-shelf technical option for aortic arch ''debranching''. More data and further improvements are required before this promising technique can be widely advocated.

Involvement of the bulge region with decreased expression of hair follicle stem cell markers in senile female cases of alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder characterized by cellular autoimmune reaction predominantly involving the bulbar portion of anagen hair follicles. In most cases of AA, the bulge stem cell area remains intact. Recently, a couple of molecules, such as keratin15 (K15) and CD200, have been identified as biomarkers of human bulge cells. Of note, an immunosuppressive molecule, CD200 is speculated to provide an immune privilege for bulge stem cells. OBJECTIVE: To investigate expression levels of stem cell markers, especially CD200, in two senile female cases of AA with unusual lymphocytic cell infiltrates surrounding both the bulge and the bulbar regions. Then, compare them with those in common AA cases without the bulge involvement. METHODS: Transverse sections containing the bulge levels were prepared from unaffected and affected lesions, respectively, from each AA group and immunohistochemical investigation using anti-K15 and CD200 antibodies was performed. Importantly, an approach to detect CD200 in paraffin sections was newly developed. Immunoreactivities of individual antibodies were compared between corresponding lesions in each patient group. RESULTS: In unaffected bulge lesions, K15 immunoreactivity was not different between bulge-involving AA and common AA groups, whilst that of CD200 was decreased in the former group. Both K15 and CD200 immunoreactivities were decreased in affected bulge lesions of bulge-involving AA compared to the bulge of common AA cases. CONCLUSION: Selective downregulation of CD200 in the bulge area could contribute to the collapse of immune privilege with resultant unusual bulge involvement in a subset of AA.

Agonist and antagonist effects of interferon alpha and beta on activation of human macrophages. Two classes of interferon gamma receptors and blockade of the high-affinity sites by interferon alpha or beta.

H2O2-releasing capacity and limited antitoxoplasma activity could be induced in human macrophages (derived from monocytes cultured greater than or equal to 5 d) but not in monocytes themselves (cells cultured less than or equal to 4 d) by a further 3-d incubation with pure natural or rIFN-alpha or -beta. More than 3 pM (10 U/ml) of these IFNs was required, with greatest effects at approximately 300 pM (10(3) U/ml). At 300 pM, H2O2-releasing capacity was enhanced 4.4 +/- 1.6-fold over medium control (mean +/- SD for natural INF-alpha, rIFN-alpha A, rIFN-alpha D, and rIFN-beta) compared to an 8.4 +/- 4.8-fold increase with rIFN-gamma (100 pM, 100 U/ml) in the same experiments. Unexpectedly, low concentrations of IFN-alpha or -beta (3 fM-300 pM) blocked induction of H2O2-releasing capacity by rIFN-gamma (10 pM), with a 50% inhibitory dose of approximately 80 fM. However, IFN-alpha or -beta (3 fM-300 pM) could not inhibit the effect of higher concentrations of rIFN-gamma (1 nM). In contrast to results with monocytes or young macrophages, Scatchard plots of binding of 125I-rIFN-gamma to mature macrophages (day 8 of culture) indicated two classes of binding sites: approximately 2,000 high-affinity sites (Kd approximately 0.43 nM) and approximately 23,000 low-affinity sites (Kd approximately 6.4 nM) per cell. Binding of 125I-rIFN-gamma to the high- but not the low-affinity sites was blocked by simultaneously added IFN-alpha or -beta, with a 50% inhibitory dose of approximately 2 U/0.25 ml (approximately 2 pM), or reversed by subsequently added IFN-alpha or -beta. Thus, differentiation of human mononuclear phagocytes in vitro is accompanied by the emergence of (a) an agonist response to submicromolar concentrations of IFN-alpha or -beta, (b) antagonism of the effect of picomolar IFN-gamma by femtomolar IFN-alpha or -beta, (c) two classes of IFN-gamma-Rs, and (d) nonstimulatory binding of IFN-alpha or -beta to the high- but not the low-affinity IFN-gamma-Rs, with higher affinity than rIFN-gamma itself. We speculate that traces of IFN-alpha or -beta derived from stromal cells, parenchymal cells, or resident macrophages may dampen the activation of mature tissue macrophages by the small amounts of IFN-gamma that diffuse from inflammatory sites into normal tissues. Such a mechanism could constrain the potentially destructive phenomenon of macrophage activation to areas where monocytes have recently immigrated and/or the concentration of IFNs is high.

Salvage esophagectomy after definitive chemoradiotherapy for synchronous double cancers of the esophagus and head-and-neck.

Head-and-neck cancer is frequently associated with esophageal cancer. Because the operative procedures for these synchronous double cancers are too invasive, definitive chemoradiotherapy tends to be applied as an initial treatment. A salvage esophagectomy for either recurrent or residual disease after definitive chemoradiotherapy in patients with such double cancer has never been reported. We reviewed 21 patients with esophageal cancer who underwent a salvage esophagectomy after definitive chemoradiotherapy. Among them, the treatment course of five patients who underwent a salvage esophagectomy for patients with synchronous double cancers of the esophagus and head-and-neck region was analyzed. Because head-and-neck cancer was well controlled after chemoradiotherapy in all five patients, a salvage esophagectomy was indicated for either recurrent or residual esophageal cancer after definitive chemoradiotherapy. Anastomotic leakage developed in four patients; however, no other complications including pulmonary complications were recognized. All of them were discharged to home and three of them are still alive without any recurrence for 20-43 months. A salvage esophagectomy should be considered as a treatment option for either recurrent or residual esophageal cancer with well-controlled head-and-neck cancer after definitive chemoradiotherapy when complete resection of the esophagus is expected.

NaCl responsive taste cells in the mouse fungiform taste buds.

Previous studies have demonstrated that rodents' chorda tympani (CT) nerve fibers responding to NaCl can be classified according to their sensitivities to the epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride-sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond specifically to NaCl, whereas AI fibers broadly respond to various electrolytes, including NaCl. These data suggest that salt taste transduction in taste cells may be composed of at least two different systems; AS and AI ones. To further address this issue, we investigated the responses to NaCl, KCl and HCl and the amiloride sensitivity of mouse fungiform papilla taste bud cells which are innervated by the CT nerve. Comparable with the CT data, the results indicated that 56 NaCl-responsive cells tested were classified into two groups; 25 cells ( approximately 44%) narrowly responded to NaCl and their NaCl response were inhibited by amiloride (AS cells), whereas the remaining 31 cells ( approximately 56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral side of taste cells had no effect on NaCl responses in the AS and AI cells. Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These findings suggest that the mouse fungiform taste bud is composed of AS and AI cells that can transmit taste information differently to their corresponding types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS cells.

Refractory response to growth factors impairs liver regeneration after hepatectomy in patients with viral hepatitis.

BACKGROUND/AIMS: Liver regeneration after surgical resection is important. The present study was designed to understand the effect of background liver damage on the rate of liver tissue regeneration after hepatectomy and the mechanism of any defective regeneration. METHODOLOGY: The subjects were 40 patients who underwent liver resection. They comprised 22 patients with chronic viral hepatitis-hepatocellular carcinoma (liver damage group) and 18 patients with hepatic metastases from colorectal cancer (normal liver group). Liver regeneration was evaluated by histopathological and immunohistochemical examination of the surgically resected tissue and by CT-scanning of the regenerated liver mass. The resected liver specimens were stained for c-met, gp-130 and nuclear factor-kappaB (NF-kappaB) proteins. RESULTS: Liver regeneration was significantly less in the liver-damage group than in the normal-liver group. Histopathological examination showed marked inflammatory cell infiltration in the liver-damage group. Expression of c-met, but not gp-130, was significantly higher on parenchymal cells of the liver-damage group than the normal-liver group. NF-kappaB expression in parenchymal liver cells was significantly higher than in non-parenchymal cells of the normal-liver group. In the liver-damage group, liver regeneration correlated negatively with the staining intensity of NF-kappaB protein in non-parenchymal cells. These findings suggest that non-parenchymal cells are constitutively activated in the damaged liver, probably explaining the refractoriness of hepatocytes to cytokine-induced proliferation after hepatectomy, in spite of increased receptor (c-met) expression. CONCLUSIONS: The refractory response of injured hepatocytes to cytokines may explain the impaired postoperative liver regeneration in patients with damaged liver.

Ral GTPase Activation by Downregulation of RalGAP Enhances Oral Squamous Cell Carcinoma Progression.

Ral small GTPases, consisting of RalA and RalB, are members of the Ras family. Their activity is upregulated by RalGEFs. Since several RalGEFs are downstream effectors of Ras, Ral is activated by the oncogenic mutant Ras. Ral is negatively regulated by RalGAP complexes that consist of a catalytic α1 or α2 subunit and its common partner ß subunit and similarly regulate the activity of RalA as well as RalB in vitro. Ral plays an important role in the formation and progression of pancreatic and lung cancers. However, the involvement of Ral in oral squamous cell carcinoma (OSCC) is unclear. In this study, we investigated OSCC by focusing on Ral. OSCC cell lines with high Ral activation exhibited higher motility. We showed that knockdown of RalGAPß increased the activation level of RalA and promoted the migration and invasion of HSC-2 OSCC cells in vitro. In contrast, overexpression of wild-type RalGAPα2 in TSU OSCC cells attenuated the activation level of RalA and inhibited cell migration and invasion. Real-time quantitative polymerase chain reaction analysis of samples from patients with OSCC showed that RalGAPα2 was downregulated in oral cancer tissues as compared with normal epithelia. Among patients with OSCC, those with a lower expression of RalGAPα2 showed a worse overall survival rate. A comparison of DNA methylation and histone modifications of the RalGAPα2 gene in OSCC cell lines suggested that crosstalk among DNA methylation, histone H4Ac, and H3K27me2 was involved in the downregulation of RalGAPα2. Thus, activation of Ral GTPase by downregulation of RalGAP expression via a potential epigenetic mechanism may enhance OSCC progression.