Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Relationship between the changes in blood flow and volume in the finger during a Braille character discrimination task.

PURPOSE: We hypothesized that skin blood flow (SBF) of fingers are modulated during concentrated finger perception and that the changes in SBF reflect fluctuations in finger volume (FV). The aim of this study, therefore, was examine the relationship between the changes in SBF and FV during Braille reading. METHODS: We measured SBF of the finger, cutaneous vascular conductance (CVC), FV, and arterial blood pressure during Braille reading performed under blind conditions in thirty healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 15 seconds using their forefinger, and to touch a blank plate as a control for the Braille discrimination procedure. RESULTS: Arterial blood pressure slightly increased during Braille reading but remained unchanged during the touching of the blank plate. SBF, CVC, and FV were reduced during Braille reading (decreased by -26%, -29%, and -0.3 mL/100 mL respectively). Furthermore, a significant relationship was observed between the changes in SBF and FV (r=.613) during Braille reading. CONCLUSION: These results suggested that SBF of fingers is modulated during concentrated finger perception, and that the variability of blood flow reflects the response in FV.

Suppressive effects of neutrophil by Salp16-like salivary gland proteins from Ixodes persulcatus†Schulze tick.

Salp16, a 16-kDa tick salivary gland protein, is known to be the molecule involved in the transmission of Anaplasma phagocytophilum, an obligate intracellular pathogen causing zoonotic anaplasmosis, from its mammalian hosts to Ixodes scapularis. Recently, the presence of A. phagocytophilum was documented in Japan and Ixodes persulcatus was identified as one of its vectors. The purpose of this study was to identify Salp16 genes in I. persulcatus and characterize their function. Two cDNA clones encoding the Salp16-like sequences were obtained from the salivary glands of fed female I. persulcatus ticks and designated Salp16 Iper1 and Iper2. Gene expression analyses showed that the Salp16 Iper genes were expressed specifically in the salivary glands and were up-regulated by blood feeding. These proteins attenuated the oxidative burst of activated bovine neutrophils and inhibited their migration induced by the chemoattractant interleukin-8 (IL-8). These results demonstrate that Salp16 Iper proteins contribute to the establishment of blood feeding as an immunosuppressant of neutrophil, an essential factor in innate host immunity. Further examination of the role of Salp16 Iper in the transmission of pathogens, including A. phagocytophilum, will increase our understanding of the tick-host-pathogen interface.

Successful treatment for Cronkhite-Canada syndrome with endoscopic mucosal resection and salazosulfapyridine.

A 79-year-old woman was referred to our hospital because numerous polyps were found in her stomach and large intestine at an ambulatory clinic. Although there were no characteristic symptoms or signs of Cronkhite-Canada syndrome (CCS), endoscopic and pathological findings indicated CCS. Moreover, colonoscopy showed two polypoid lesions (Is type), which appeared neoplastic by magnifying observation with image-enhanced endoscopy (IEE), in the ascending colon. Histologically, the resected specimens revealed tubular adenomas arising in the CCS inflammatory polyps. Remarkable remission of the polyps and edematous mucosa in the stomach and colon was seen after 8 months of administration of salazosulfapyridine (SASP) (3 g/day). Another adenoma was detected and removed endoscopically in the sigmoid colon. This is the first report to describe an asymptomatic case of CCS probably detected in the early phase of the disease, by magnifying IEE which enabled detection and treatment for associated colonic adenomas. SASP was effective in eradication of the inflammatory polyposis, and an additional adenoma was successfully found and removed by surveillance colonoscopy thereafter.

Glue embolization for gastroduodenal ulcer bleeding: contribution to hemodynamics and healing process.

BACKGROUND: Although the morbidity of bowel ischemic events after glue embolization has been suggested, a causal relationship between glue and ischemia has not been clearly established. PURPOSE: To evaluate the efficiency and safety of transcatheter arterial embolization with n-butyl cyanoacrylate (NBCA-TAE) for upper gastrointestinal hemorrhage (GIH). MATERIAL AND METHODS: Between October 2006 and October 2012, 21 patients with upper GIH underwent NBCA-TAE, and endoscopic data were obtained within 30 days of follow-up. Shock index prior to and immediately after NBCA-TAE were compared to determine changes in hemodynamics. Days to Forrest type III, as assessed by follow-up endoscopy, was used as an indicator of the healing process. Other clinical outcomes included days for starting ingestion and for hospital discharge. RESULTS: Sixteen gastric and five duodenal ulcers, classified into Forrest type I, were treated. Immediate hemostasis was achieved in all the patients, and no re-bleeding occurred within the follow-up period. Shock index significantly (P < 0.001) improved from before (0.99 ± 0.076) to immediately after NBCA-TAE (0.67 ± 0.038). Sequential mucosal healing processes were observed in all the patients, and the number of days to Forrest type III was 9.6 ± 7.1. The number of days for starting ingestion and hospital discharge was 9.0 ± 4.5 and 15 ± 7.7 days, respectively. CONCLUSION: NBCA-TAE is an effective and safe method for the control of nonvariceal upper GIH, in terms of contribution to hemodynamics and healing process of the gastroduodenal mucosa.

Relationship between abdominal fat content and avian uncoupling protein gene expression in skeletal muscle of Japanese quail Coturnix japonica.

1. The genetic architecture of the avian uncoupling protein (avUCP) was investigated and the relationship between avUCP gene expression and the amount of abdominal fat of Japanese quail was determined by quantitative real-time PCR. 2. The Japanese quail avUCP gene consists of six exons and five introns. Sequences of nucleotides and amino acids were 94·6% and 86·0% identical to those of the chicken avUCP gene, and phylogenetic analysis showed that the Japanese quail avUCP gene consists of the same clusters as the chicken and turkey avUCP. 3. Expression of the avUCP gene was significantly higher in the Pectoralis major (1·28 ± 0·24) than in the Biceps femoris (0·63 ± 0·14). 4. A positive correlation coefficient between the avUCP gene expression in the Pectoralis major and Biceps femoris was observed (r = 0·79, P = 0·02), whereas a negative correlation coefficient was observed between the abdominal fat percentage (AFP) and gene expression in both the Pectoralis major (r = -0·82, P = 0·01) and Biceps femoris (r = -0·61, P = 0·11). 5. The avUCP gene was associated with the accumulation of abdominal fat in Japanese quail and it was concluded that modulation of avUCP gene expression could be utilised to control abdominal fat accumulation in poultry.

Kinetics of regulatory dendritic cells in inflammatory responses during Trypanosoma evansi infection.

Trypanosoma evansi (T. evansi) causes a wasting disease in almost all mammals. Trypanosoma evansi infection gives rise to the inflammatory responses that contribute to the development of inflammation-associated tissue injury. To determine what kinds of inflammatory molecules play roles in the pathogenicity of T. evansi infection, polymerase chain reaction array analysis was performed on samples from the infected and uninfected mice. The inflammatory cytokine and chemokine storm, caused mainly by macrophages, was observed. On the other hand, the expression levels of Ccl8 and Il10 in splenocytes were also markedly increased. These results suggested an augmentation in the number and activity of regulatory dendritic cells (DCs). Therefore, the kinetics of regulatory DCs in T. evansi-infected mice were investigated. During T. evansi infection, the regulatory DCs became prevalent, with reducing the amount of inflammatory DCs. Interestingly, when the regulatory DCs were implanted into T. evansi-infected mice, the survival was prolonged, and the expression levels of inflammatory molecules were suppressed. Taken together, these results showed that a subset of regulatory DCs acted as a potential regulator of the inflammatory responses.

Molecular cloning and characterization of Th1 and Th2 cytokines of African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) has been implicated as the reservoir of several bovine infectious agents. However, there is insufficient information on the protective immune responses in the African buffalo, particularly in infected animals. In this study, we analysed Th1 cytokines IL-2 and IFN-γ, and Th2 cytokines IL-4 and IL-10. The cloned cDNA of IL-2, IL-4, IL-10 and IFN-γ contained an open reading frame of 468, 501, 408 and 540 nucleotides, encoding polypeptides of 155, 166, 135 and 179 amino acids, respectively. Nucleotide sequence homology of IL-2, IFN-γ and IL-4 was more than 98% between the African buffalo and cattle, which resulted in identical polypeptides. Meanwhile, IL-10 gene of African buffalo and cattle had 95% homology in nucleotide sequence, corresponding to thirteen amino acid residues substitution. Cysteine residues and potential glycosylation sites were conserved within the family Bovinae. Phylogenetic analyses including cytokines of the African buffalo placed them within a cluster comprised mainly of species belonging to the order Artiodactyla, including cattle, water buffalo, sheep, goat, pig and artiodactyl wildlife. A deeper understanding of the structure of these cytokines will shed light on their protective role in the disease-resistant African buffalo in comparison with other closely related species.

Revascularization by percutaneous transluminal angioplasty improved abruptly deteriorated ischaemic symptoms in cutaneous polyarteritis nodosa.

We report a patient with cutaneous polyarteritis nodosa, who had a 3-year history of recurrent leg and foot ulcers. Symptoms of ischaemia in the left foot, including severe pain, coldness, paraesthesia and violaceous discoloration, deteriorated abruptly, because of complete occlusion of the left anterior tibial artery. The occluded segment was revascularized by percutaneous transluminal angioplasty, resulting in a dramatic improvement in the ischaemic symptoms.

Prostaglandin-related immune suppression in cattle.

Prostaglandins (PGs) are lipid mediators derived from arachidonic acid by several enzymes including cyclooxygenase (COX)-1 and COX-2. We have previously shown that PGE2 regulates immune responses, such as Th1 cytokine production and T-cell proliferation, in cattle. However, it is still unclear whether other PGs are involved in the regulation of immune responses in cattle. Here, immunosuppressive profiles of PGs (PGA1, PGB2, PGD2, PGE2, PGF1α and PGF2α) were firstly examined using bovine peripheral blood mononuclear cells (PBMCs). In addition to PGE2, PGA1 significantly inhibited Th1 cytokine production from PBMCs in cattle. Further analyses focusing on PGA1 revealed that treatment with PGA1 in the presence of concanavalin A (con A) downregulated CD69, an activation marker, and IFN-γ expression in both CD4+ and CD8+ T cells. Sorted CD3+ T cells stimulated with con A were cultivated with PGA1, and IFN-γ and TNF-α concentrations decreased upon PGA1 treatment. Taken together, these results suggest that the treatment with PGA1in vitro inhibits T-cell activation, especially Th1 cytokine production, in cattle.

Antimicrobial activity of sodium citrate against Streptococcus pneumoniae and several oral bacteria.

AIMS: The aim of this study is to assess the antibacterial activity of sodium citrate against Streptococcus pneumoniae and several oral bacteria. METHODS AND RESULTS: The antibacterial activity was determined by broth microdilution method. The results showed that although Enterocuccus faecium OB7084 and Klebsiella pneumoniae OB7088 had high tolerance to sodium citrate, several oral bacteria including Fusobacterium nucleatum JCM8532(T) , Streptococcus mutans JCM5705(T) and Strep. pneumoniae NBRC102642(T) were susceptible. Furthermore, the bactericidal activity of sodium citrate against Strep. pneumoniae NBRC102642(T) was not influenced by pH in the range of 5·0-8·0, whereas that of sodium lactate was weakened at neutral or weak alkaline pH. When Strep. pneumoniae NBRC102642(T) was treated with sodium citrate for 2 h, many burst cells were observed. However, addition of MgCl(2) or CaCl(2) to an assay medium weakened the antimicrobial activity although ZnCl(2) or MnCl(2) did not influence. CONCLUSIONS: Independent of pH, sodium citrate inhibited the growth of oral bacteria, which suggests that the mechanism is different from that of sodium lactate. SIGNIFICANCE AND IMPACT OF THE STUDY: The results presented in this study would be available for understanding the antimicrobial property of sodium citrate.

Inter- and intra-rater reliability in fibroptic endoscopic evaluation of swallowing.

Fibroptic endoscopic evaluation of swallowing (FEES) is a useful way for dentists to evaluate oropharyngeal dysfunction. However, no study has paid attention to inter- and intra-rater reliability of FEES evaluation about oropharyngeal dysfunction. The purpose of this study is to verify whether dentist who trained and experienced for evaluation of dysphagia could diagnose oropharyngeal function with FEES. Nine dentists independently evaluated FEES images of 10 cases four times each. At first, evaluators performed the first evaluation without consulting the evaluative criteria. Subsequently, evaluators independently re-evaluated at 1-week intervals for three consecutive weeks, consulting the evaluative criteria. And then, inter- and intra-rater reliability was calculated. Cohen's Kappa was used to assess reliability. The results found that overall inter-rater reliability was 0·35±0·04 (first evaluation), 0·45±0·05 (s), 0·44±0·05 (third) and 0·46±0·04 (fourth). Most of inter-rater reliability related to aspiration was moderate to high, but lower for categories that evaluated timing of swallowing and mastication. In contrast, intra-rater reliability was moderate to high for overall categories, at 0·53±0·04 (first vs. second evaluation), 0·55±0·04 (first vs. third), 0·53±0·04 (first vs. fourth), 0·55±0·03 (second vs. third), 0·60±0·03 (second vs. fourth) and 0·78±0·03 (third vs. fourth). FEES is reliable for experienced dentists to diagnose oropharyngeal function. Moreover, repeated evaluation with the aids of evaluative criteria is useful to improve the reliability of FEES.

Susceptibility of patients receiving chemotherapy for haematological malignancies to scabies.

BACKGROUND: Scabies is a contagious dermatosis. The risk factors for its transmission remain unclear. A scabies outbreak, involving patients who were receiving chemotherapy for haematological malignancies, occurred at our hospital. METHODS: The outbreak population was analysed to determine whether the incidence of scabies was higher among contact patients receiving chemotherapy for haematological malignancies. RESULTS: A patient with crusted scabies was the index case, and 18 of 78 contact healthcare workers (HCWs) and 22 of 135 contact patients were diagnosed with classical scabies. Ten of 17 contact patients with haematological malignancies and 12 of 118 contact patients with other diseases were infected with scabies. The incidence rate was significantly higher among the patients with haematological malignancies (P<0.001). The patients with haematological malignancies had a significantly lower mean minimum neutrophil count than those with other diseases (1159/µL vs 3761/µL, P=0.0012). Most haematological patients did not require special nursing assistance, suggesting that the higher incidence of scabies among these patients resulted from their immunodeficiency rather than greater skin-to-skin contact with infected HCWs. CONCLUSION: Our study suggests that patients receiving chemotherapy for haematological malignancies are more susceptible to scabies than patients with other diseases, and require stricter protection.

Evaluation of two mineral trioxide aggregate compounds as pulp-capping agents in human teeth.

AIM: The present randomized, controlled prospective study evaluated the histomorphological response of human dental pulps capped with two grey mineral trioxide aggregate (MTA) compounds. METHODOLOGY: Pulp exposures were performed on the occlusal floor of 40 human permanent pre-molars. The pulp was capped either with ProRoot (Dentsply) or MTA-Angelus (Angelus) and restored with zinc oxide eugenol cement. After 30 and 60 days, teeth were extracted and processed for histological examination and the effects on the pulp were scored. The data were subjected to Kruskal-Wallis and Conover tests (alpha = 0.05). RESULTS: In five out of the 40 teeth bacteria were present in pulp tissue. No significant difference was observed between the two materials (P > 0.05) in terms of overall histological features (hard tissue bridge, inflammatory response, giant cells and particles of capping materials). Overall, 94% and 88% of the specimens capped with MTA-Angelus and ProRoot, respectively, showed either total or partial hard tissue bridge formation (P > 0.05). CONCLUSIONS: Both commercial materials ProRoot (Dentsply) and MTA-Angelus (Angelus) produced similar responses in the pulp when used for pulp capping in intact, caries-free teeth.

Neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast--comparative clinicopathological study of 20 NE-DCIS cases and 274 non-NE-DCIS cases.

UNLABELLED: Kawasaki T, Nakamura S, Sakamoto G, Murata S, Tsunoda-shimizu H, Suzuki K, Takahashi O, Nakazawa T, Kondo T & Katoh R (2008) Histopathology53, 288-298Neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast - comparative clinicopathological study of 20 NE-DCIS cases and 274 non-NE-DCIS cases Aims: To clarify the clinicopathological significance of breast neuroendocrine ductal carcinoma in situ (NE-DCIS), i.e. DCIS in which >50% of cells immunohistochemically express NE markers (chromogranin A and/or synaptophysin), 20 NE-DCIS were studied and the findings compared with those of 274 non-NE-DCIS. METHODS AND RESULTS: NE-DCIS accounted for 6.8% of all DCIS. Mean patient age was 50.4 years for NE-DCIS and 49.6 years for non-NE-DCIS (P = 0.66). The main clinical presentation of NE-DCIS was a bloody nipple discharge, seen in 72%, significantly different from the 5% in non-NE-DCIS cases (P < 0.01). Carcinoma was preoperatively diagnosed in 67% of NE-DCIS and 95% of non-NE-DCIS cases (P < 0.01). NE-DCIS was histologically characterized by a predominantly solid growth of cancer cells with fine-granular cytoplasm and ovoid, or occasionally spindle-shaped nuclei. A well-developed vascular network was also common. Nuclear grades and Van Nuys classification were significantly lower for NE-DCIS than for non-NE-DCIS (P < 0.01). The mean MIB-1 labelling index was 4.3% in NE-DCIS and 8.1% in non-NE-DCIS (P < 0.01). Furthermore, NE-DCIS cases had significantly higher oestrogen and progesterone receptor and lower HER2 scores than non-NE-DCIS cases (P < 0.01). CONCLUSIONS: NE-DCIS has characteristic clinicopathological features and can, therefore, be regarded as a distinct variant of DCIS.

Response of human dental pulp capped with MTA and calcium hydroxide powder.

OBJECTIVES: To compare the response of human dental pulp capped with a mineral trioxide aggregate (MTA) and Ca(OH)2 powder. METHODS AND MATERIAL: Pulp exposures were performed on the occlusal floor of 40 permanent premolars. The pulp was then capped with either Ca(OH)2 powder (CH) or MTA and restored with resin composite. After 30 days (groups CH30 and MTA30) and 60 days (groups CH60 and MTA60), the teeth were extracted and processed for HE and categorized in a histological score system. The data were subjected to Kruskal-Wallis and Conover tests (alpha = 0.05). RESULTS: In regard to dentin bridge formation, CH30 showed a tendency towards superior performance compared to MTA30 (p > 0.05), although the products showed comparable results at day 60. In the item "Inflammation" and "General State of the Pulp" (p > 0.05), CH showed a tendency towards presenting a higher inflammatory response. In the item "Other Pulpal Findings," MTA and Ca(OH)2 showed equal and excellent performance after 30 and 60 days (p > 0.05). CONCLUSION: After 30 days, Ca(OH)2 powder covered with calcium hydroxide cement showed faster hard tissue bridge formation compared to MTA. After 60 days, Ca(OH)2 powder or MTA materials showed a similar and excellent histological response with the formation of a hard tissue bridge in almost all cases with low inflammatory infiltrate.

Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome.

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.