Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

Optimization of steroid injection intervals for prevention of stricture after esophageal endoscopic submucosal dissection: A randomized controlled trial.

BACKGROUND: Esophageal endoscopic submucosal dissection enables en bloc resection of large superficial esophageal cancer; however, this procedure may induce severe stricture. Intralesional steroid injection is an effective treatment for prevention of stricture after endoscopic resection; however, there have been no studies assessing the duration of such treatment. The aim of this study was to reduce treatment duration and to evaluate the effectiveness of weekly and biweekly steroid injections in preventing esophageal stricture after endoscopic resection. PATIENTS METHOD: We performed a randomized controlled trial comparing patients receiving weekly or biweekly intralesional triamcinolone injections. Patients with a mucosal defect greater than 75% (3/4) of the luminal circumference after esophageal endoscopic submucosal dissection for superficial esophageal cancers were enrolled. The primary endpoint was the duration of steroid injection treatment. RESULTS: The median duration of treatment was 37.0 days in the weekly group and 34.2 days in the biweekly group (P = 0.059). Among patients with a mucosal defect larger than 50 mm, there was a significant difference in the median duration of treatment between the weekly and biweekly groups (42.5 days vs 29.0 days, P = 0.013). CONCLUSION: Biweekly steroid injection of triamcinolone reduces treatment duration, particularly in those with mucosal defects larger than 50 mm. (Acta gastro-enterol. belg., 2016, 79, 315-320).

Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

Spatiotemporal expression patterns of doublesex and mab-3 related transcription factor 1 in the chicken developing gonads and Mullerian ducts.

Sex of birds is genetically determined by the inheritance of sex chromosomes (ZZ for male and ZW for female), and the Z-linked gene named doublesex and mab-3 related transcription factor 1 (DMRT1) is a candidate sex-determining gene in avian species. However, the mechanisms underlying sex determination in birds are not yet understood, and the expression patterns of the DMRT1 protein in urogenital tissues have not been identified. In the current study, we used immunohistochemistry to investigate the detailed expression patterns of the DMRT1 protein in the urogenital systems (including Müllerian ducts) in male and female chicken embryos throughout embryonic development. Gonadal somatic cells in the male indifferent gonads showed stronger expressions of DMRT1 compared with those in the female indifferent gonads well before the presumptive period of the sex determination, and Sertoli cells forming testicular cords expressed DMRT1 in the testes after sex determination. Germ cells expressed DMRT1 equally in males and females after sex determination. The expression was continuous in males, but in females it gradually disappeared from the germ cells in the central part of the cortex of the left ovary toward both edges. The DMRT1 was also detected in the tubal ridge, which is a precursor of the Müllerian duct, and at the mesenchyme and outermost coelomic epithelium of the Müllerian duct in both sexes. Strong expression was observed in the males, but it was restricted to coelomic epithelium after the regression of the duct started. Thus, we observed the detailed spatiotemporal expression patterns of DMRT1 in the developing chicken urogenital systems throughout embryonic development, suggesting its various roles in the development of urogenital tissues in the chicken embryo.

Site differences of Toll-like receptor expression in the mucous epithelium of rat small intestine.

Toll-like receptors (TLRs) are known to recognize pathogen-associated molecular patterns and might function as receptors to detect microbes. In this study, the distribution of TLR-2, -4 and -9 were immunohistochemically investigated in the rat small intestine. As a result, TLR-2 was detected in the striated borders of villous columnar epithelial cells throughout the small intestine, except for the apices of a small number of intestinal villi. TLR-4 and -9 were detected in the striated borders of the villous columnar epithelial cells only in the duodenum. TLR-4-immunopositive minute granules were found in the apical cytoplasms of epithelial cells, subepithelial spaces and blood capillary lumina. TLR-2 and -4 were detected in the striated borders of undifferentiated epithelial cells and in the luminal substances of the intestinal crypts throughout the small intestine, but TLR-9 was not detected in the crypts throughout the small intestine. Only TLR-4 was detected in the secretory granules of Paneth cells in both the jejunal and ileal intestinal crypts. These findings suggest that duodenal TLRs might monitor indigenous bacteria proliferation in the upper alimentary tract, that TLR-2 might also monitor the proliferation of colonized indigenous bacteria throughout the small intestine, that the lack of TLR-2 at the villous apices might contribute to the settlement of indigenous bacteria, and that TLR-2 and -4 are secreted from intestinal crypts.

Immunohistochemical study of the apoptosis process in epidermal epithelial cells of rats under a physiological condition.

Epidermal homeostasis is maintained by both epithelial proliferation in the stratum basale (SB) and the apoptosis of epithelial cells under physiological conditions. In this study, the induction and regulation mechanisms of epidermal apoptosis were immunohistochemically investigated in the epidermis from Wistar rat's palm and foot pad by using several apoptotic related proteins under a physiological condition. The results showed that Fas and Fas-L were expressed in cellular membranes of the stratum spinosum (SS), whereas TNF-R1 did not show any membranous expression in any epidermal layers. TNF-α was not observed in the epidermis. Caspase-10, cleaved caspase-3 and DNase-1 were found in the epithelial cytoplasms from the SS to stratum granulosum (SG), whereas caspase-8 was not detected in the epidermis. XIAP and Bak were found in the cytoplasm from the SS to SG, and the intensity of Bak-positivity was stronger in the SG than the SS, whereas Bid, Apaf-1 and cleaved caspase-9 were restricted in the SG. Homogenous cytoplasmic immunoreactivity of Bcl-2 was found in the SB and the intensity was gradually decreased from the SB to the SG. The granular-cytoplasmic immunopositivity of cytochrome C gradually altered into homogenous cytoplasmic expression in the upper half of the SG. Single-stranded DNA was rarely detected in the upper portion of the SG. These results suggest that epidermal apoptosis is induced by the interaction between Fas and Fas-L and the activation of caspase-10, and might initially proceed through a mitochondrial-independent pathway, and that a mitochondrial-dependent pathway finally accelerated under physiological conditions.

Both N-terminal and C-terminal regions of steroid sulfatase are important for enzyme activity.

Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes desulfation of 3beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an inherited skin disorder caused by deficiency of STS enzyme activity. We previously reported a case in which XLI with a one-base change in the STS gene and variation in amino acid Q560P developed. In this study, we performed molecular analysis to determine the importance of terminal regions of STS and the effect of mutant STS on STS enzyme activity. To examine the effect of terminal truncated STS on the enzyme activity, N- and C-terminal truncated STS expression vectors were transfected into COS-1 cells. The activity of truncated STS lacking the N-terminal regions declined, and the activity of C-terminal-truncated STS declined with extension of the truncated C-terminal region. Although the results of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C-terminal-truncated STS (deltaC2 (1-559)) had no effects on protein synthesis and degradation, the mutant STS and C-terminal-truncated STS have dominant negative effect on STS enzyme activity when the STS mutant or truncated STS protein and a wild-type STS protein coexist in cells. Results of coprecipitation of the truncated STS with an STS-FLAG fusion protein showed that STS formed a dimer conformation in cells. In this study, we have shown that both the N-terminal region and C-terminal region are important for STS enzyme activity. The C-terminal mutant has a dominant negative effect on wild-type STS.

Myofibrosarcoma of the bone: a clinicopathologic study.

Myofibroblastic tumors are fairly recently established soft tissue neoplasms. Although most of them appear to be benign, myofibrosarcoma of the soft tissue, seemingly their malignant counterpart, have been reported. We describe the clinicopathologic and radiologic features of four cases of myofibrosarcoma arising from the bone. All but one of the patients were women ranging in age from 60 to 71 years. Two tumors occurred in the metaphyses of distal femurs and the others arose in the iliac bones. On radiologic examination all tumors exhibited well-demarcated lytic destructive lesions without periosteal reaction. Two tumors were localized in the bone, whereas the other two extended into surrounding soft tissues. Histologically, all tumors were composed principally of a mixture of a cell-rich fascicular area and a hypocellular fibrous area. In the former area tumor cells had rather eosinophilic spindle-shaped wavy cytoplasm and were arranged in interlacing fascicles and small storiform patterns with variable numbers of inflammatory cells. Tumors occasionally showed prominent pleomorphism, and large cells with hyperchromatic nuclei were seen. In contrast, hypocellular areas had various features, including collagenous, hyalinous scar-like and rarely keloid-like areas. Focal coagulation necroses were present in all but one tumor. Immunohistochemically, the tumors were positive for vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin, whereas all of them were negative for high molecular weight caldesmon. On follow-up there was one fatal case with distant metastases, whereas the clinical courses of other cases after wide resection were excellent. Myofibrosarcoma of the bone has distinctive histopathologic features, which should be distinguished from those of other bone tumors with myoid differentiation.

Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase.

Cyclic ADP-ribose (cADPR), an endogenous modulator of ryanodine receptor Ca(2+)-releasing channels, is found in various tissues. Cytosolic injection of cADPR induces an elevation of intracellular Ca(2+) concentrations or potentiates Ca(2+) increases. cADPR facilitates neurotransmitter or insulin release and modifies ionic currents. cADPR is synthesized by ADP-ribosyl cyclase and is metabolized by cADPR hydrolase. ADP-ribosyl cyclase activity is up-regulated by nitric oxide/cyclic GMP-dependent phosphorylation or receptor stimulation via G-proteins within membranes. These findings suggest that cADPR is a second messenger in cellular Ca(2+) signaling. However, many intriguing issues remain to be addressed before this identity is confirmed.

Lens culinaris agglutinin-reactive alpha-fetoprotein, an alternative variant to alpha-fetoprotein in prenatal screening for Down's syndrome.

BACKGROUND: Three serum tests, alpha-fetoprotein (AFP), human chorionic gonadotrophin and unconjugated oestriol, are now widely used for screening for Down's syndrome. Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is a variant of alpha-fetoprotein with alpha1-->6 fucose appended to the reducing terminal N-acetylglucosamine. It is the most prominent AFP detected in the serum of patients with hepatocellular carcinoma. METHODS: We investigated microheterogeneities of the carbohydrate chain on AFP in fetal liver tissues, amniotic fluids and maternal sera obtained from pregnancies with Down's syndrome using lectin affinity electrophoresis with four lectins. The percentages of AFP-L3 in maternal sera from 22 Down's syndrome and 227 unaffected pregnancies were determined. RESULTS: Unlike the case with AFP concentration, the percentage of AFP-L3 in maternal serum and amniotic fluid was similar, and apparently not influenced by membrane permeability. Knowing the percentage of AFP-L3 in maternal serum was effective for discriminating between Down's syndrome-affected pregnancies and unaffected pregnancies. The percentage of AFP-L3 in maternal serum identified 55% of Down's syndrome cases with a 5% false-positive rate. CONCLUSIONS: AFP-L3 should be an effective replacement for AFP in prenatal Down's syndrome screening.

Pseudosarcomatous myofibroblastic tumor and myosarcoma of the urogenital tract.

OBJECTIVE: Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis. METHODS: We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, alpha-smooth muscle actin, high-molecular-weight caldesmon, and myogenin. RESULTS: Desmin, muscle-specific actin, and alpha-smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas. CONCLUSION: High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.

Endometrioid adenocarcinoma arising from adenomyosis: report and immunohistochemical analysis of an unusual case.

A case of endometrioid adenocarcinoma arising from adenomyosis is reported. The patient was a 53-year-old woman who complained of vulvar itching. Smear cytology of the endometrium revealed adenocarcinoma. Magnetic resonance imaging of the pelvis revealed a lesion with a slightly high intensity in the uterine fundus on a T2-weighted image. Semiradical total hysterectomy and bilateral adnexectomy were performed, followed by chemotherapy. Histologically, the lesion in the uterine fundus was composed mostly of adenocarcinoma with stromal invasion. There were many adenomyotic foci in and around the carcinoma, including some showing transition to adenocarcinoma. There was no malignant finding in the normally situated endometrium. The carcinoma invaded in the myometrium, involving the uterine serosa, but no dissemination to the peritoneal cavity was found. The carcinoma was, therefore, considered to be endometrioid adenocarcinoma arising from adenomyosis. Immunohistochemistry showed expression of p53 oncoprotein and Ki-67 antigen in the carcinoma cells. The value of immunohistochemistry in predicting prognosis is discussed.

Signal transduction from bradykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase.

Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and beta-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from beta-NAD+. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cbeta and beta-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca2+ from the type II ryanodine receptors as well as to facilitate Ca2+ influx through voltage-dependent Ca2+ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G(q/11)-coupled receptors can control cADPR-dependent modulation in Ca2+ signaling.

Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling.

Cyclic ADP-ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca2+ concentration ([Ca2+]i), and/or secondarily potentiates [Ca2+]i increases that are the result of depolarization-induced Ca2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K+ currents or elicits Ca2+-dependent inward currents. cADPR is synthesized by both membrane-bound and cytosolic forms of ADP-ribosyl cyclase in neuronal cells. cADPR hydrolase activity is weak in the membrane fraction, but high in the cytoplasm. Cytosolic ADP-ribosyl cyclase activity is upregulated by nitric oxide/cyclic GMP-dependent phosphorylation. Stimulation of muscarinic and beta-adrenergic receptors activates membrane-bound ADP-ribosyl cyclase via G proteins within membranes of neuronal tumor cells and cortical astrocytes. These findings strongly suggest that cADPR is a second messenger in Ca2+ signaling in the nervous system, although many intriguing issues remain to be addressed before this identity is confirmed.

Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis.

A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW. The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk). Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy.

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.

Dumb-bell-type teratoma in the lumbar spine.

We report a case of a lumbar teratoma in a 50-year-old woman. The teratoma showed a dumb-bell-type expansion at the level of the left L3/4 foramen with massive erosion of the L3 vertebral body. MRI revealed inhomogeneous signal changes in the tumor, which were histologically compatible with a mixture of bone, muscle, fat, and cyst containing sebaceous material. Complete resection of the tumor and spinal arthrodesis with pedicle screw fixation was necessary to obtain stability of the affected spinal segment.