Giant Magnetoresistance in Bulk, Liquid-quenched Ribbon and Film Granular Alloys

Magnetoresistance has been investigated for bulk, liquid-quenched ribbon and film noble metal(NM)-rich granular alloys. Solid solutions were obtained in the water- , liquid- and vapor-quenched state and nano-structured magnetic precipitates in NM-rich matrix were evolved by subsequent heat treatments. After aging, the giant magnetoresistance (GMR) is observed in these bulk, liquid quenched ribbon and film granular alloys. In particular, the room temperature value of Magnetoresistance (MR) ratio of 5 % in the Co_Au_ bulk granular alloy aged at 300 ℃ for 1 h is larger than that reported in Co/Au multilayers. The Co_Cu_ alloy ribbons aged at 500 ℃ for 90 min exhibits the MR ratio as large as 6.3 % at room temperature in a field of 15 kOe. Small amounts of Ni improve the MR ratio. Especially, the Co_Ni_5Cu_ alloy ribbons aged at 500 ℃ for 60 min exhibits the ratio of 7.6 % larger than the value of the aged Co_Cu_ ribbon. Furthermore, the anisotropy in GMR in bulk Fe_5Ni_Cu_ alloy aged at 500 ℃ for 170 min is obtained by compression

Human salivary protein-derived peptides specific-salivary SIgA antibodies enhanced by nasal double DNA adjuvant in mice play an essential role in preventing Porphyromonas gingivalis colonization : an in-vitro study

Background: We previously showed that fimbriae-bore from Poryphyromonas gingivalis (Pg), one of the putative periodontopathogenic bacteria specifically bound to a peptide domain (stat23, prp21) shared on statherin or acidic proline-rich protein 1 (PRP1) molecule of human salivary proteins (HSPs). Here, we investigated whether the nasal administration of DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 as double DNA adjuvant (dDA) with stat23 and prpr21 induces antigen (Ag)-specific salivary secretory IgA (SIgA) antibodies (Abs) in mice. Further, we examined that stat23- and prpr21-specific salivary SIgA Abs induced by dDA have an impact on Pg-binding to human whole saliva-coated hydroxyapatite beads (wsHAPs). Material and methods: C57BL/6N mice were nasally immunized with dDA plus sta23 or/and prp21 peptide as Ag four times at weekly intervals. Saliva was collected one week after the final immunization and was subjected to Ag-specific ELISA. To examine the functional applicability of Ag-specific SIgA Abs, SIgA-enriched saliva samples were subjected to Pg binding inhibition assay to wsHAPs. Results: Significantly elevated levels of salivary SIgA Ab to stat23 or prp21 were seen in mice given nasal stat23 or prp21 with dDA compared to those in mice given Ag alone. Of interest, mice nasally given the mixture of stat23 and prp21 as double Ags plus dDA, resulted in both stat23- and prp21-specific salivary SIgA Ab responses, which are mediated through significantly increased numbers of CD11c+ dendritic cell populations and markedly elevated Th1 and Th2 cytokines production by CD4+ T cells in the mucosal inductive and effector tissues. The SIgA Ab-enriched saliva showed significantly reduced numbers of live Pg cells binding to wsHAPs as compared with those in mice given double Ags without dDA or naïve mice. Additionally, saliva from IgA-deficient mice given nasal double Ags plus dDA indicated no decrease of live Pg binding to wsHAPs. Conclusion: These findings show that HSP-derived peptides-specific salivary SIgA Abs induced by nasal administration of stat23 and prp21 peptides plus dDA, play an essential role in preventing Pg attachment and colonization on the surface of teeth, suggesting a potency that the SIgA may interrupt and mask fimbriae-binding domains in HSPs on the teeth

A nasal double DNA adjuvant system induces atheroprotective IgM antibodies via dendritic cell-B-1a B cell interactions

We previously demonstrated that the dendritic cell (DC)-targeting nasal double DNA adjuvant system, which consists of a DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 (CpG ODN), elicits specific immune responses to various antigens in the mucosal and systemic compartments. Here, we investigated, using phosphorylcholine (PC)-conjugated keyhole limpet hemocyanin (PC-KLH) as an antigen, whether the nasal double DNA adjuvant system induces protective immunity to atherosclerosis in apolipoprotein E-deficient (ApoE KO) mice. Further, we assessed the molecular and cellular mechanisms in the induction of anti-PC-specific immune responses. Nasal immunization with PC-KLH plus pFL and CpG ODN enhanced induction of PC-specific IgM in plasma, peritoneal fluids, and nasal washes when compared with mice administered PC-KLH alone. Of importance, these antibodies exhibited highly specific binding to the PC molecule, and dose-dependent binding to anti-T15 idiotype (AB1-2). Twelve weeks after the last immunization, the nasal double DNA adjuvant system with PC-KLH resulted in a reduction of atherogenesis in the aortic arch of ApoE KO mice. Therefore, we next assessed immunocytological mechanism to induce these antibodies. The nasal double DNA adjuvant system with PC-KLH resulted not only in significantly increased frequencies of CD11c+ DCs in the spleen, peritoneal cavity (PEC), and nasopharyngeal-associated lymphoid tissues (NALT), but also significantly increased expression of a proliferation-inducing ligand and B-cell-activating factor by CD11c+ DCs. In addition, the double DNA adjuvant system induced significantly increased numbers of B-1 B cells in the spleen, PEC, and NALT, and increased expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor on CD5+ B220+ (B-1a) B cells. These findings demonstrated that the nasal double DNA adjuvant system with PC-KLH resulted in the induction of T15-like antibodies in the mucosal and systemic lymphoid tissues through interaction between DCs and B-1a B cells, and inhibited the progression of atherogenesis

Median nerve neuropathy in the forearm due to recurrence of anterior wrist ganglion that originates from the scaphotrapezial joint: Case Report

<p>Abstract</p> <p>Background</p> <p>Median nerve neuropathy caused by compression from a tumor in the forearm is rare. Cases with anterior wrist ganglion have high recurrence rates despite surgical treatment. Here, we report the recurrence of an anterior wrist ganglion that originated from the Scaphotrapezial joint due to incomplete resection and that caused median nerve neuropathy in the distal forearm.</p> <p>Case presentation</p> <p>A 47-year-old right-handed housewife noted the appearance of soft swelling on the volar aspect of her left distal forearm, and local resection surgery was performed twice at another hospital. One year after the last surgery, the swelling reappeared and was associated with numbness and pain in the radial volar aspect of the hand. Magnetic resonance imaging revealed that the multicystic lesion originated from the Scaphotrapezial joint and had expanded beyond the wrist. Exploration of the left median nerve showed that it was compressed by a large ovoid cystic lesion at the distal forearm near the proximal end of the carpal tunnel. We resected the cystic lesion to the Scaphotrapezial joint. Her symptoms disappeared 1 week after surgery, and complications or recurrent symptoms were absent 13 months after surgery.</p> <p>Conclusions</p> <p>A typical median nerve compression was caused by incomplete resection of an anterior wrist ganglion, which may have induced widening of the cyst. Cases with anterior wrist ganglion have high recurrence rates and require extra attention in their treatment.</p

Clinical Significance of Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory Tract

We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections

Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic Tolerance Reduction

Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized P. aeruginosa quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against P. aeruginosa PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic P. aeruginosa biofilm infections

Activation of 1-nitropyrene by nitroreductase increases the DNA adduct level and mutagenicity

1-Nitropyrene (1-NP) is a mutagenic nitro compound in the environment. We studied correlations between the mutagenicity of 1-NP for three strains of Salmonella typhimurium, the activity of bacterial nitroreductases and the amount of 1-NP-derived DNA adducts. Bacterial strains used in this study were S. typhimurium strains TA98, nitroreductase-less mutant TA98NR and YG1021 carrying a nitroreductase-producing plasmid. The mutagenicity of 1-NP was measured using the Ames assay, and the nitroreductase activities of these strains were assayed by quantification of 1-aminopyrene produced from 1-NP. The DNA adducts were measured by the 32P-postlabeling method. Among the three bacterial strains, strain YG1021 was the highest in mutagenicity of 1-NP, the nitroreductase activity and the DNA adduct level. However, S. typhimurium strain TA98NR had the lowest values of these three parameters. Nitroreductase activity, DNA adduct level and mutagenicity were strongly correlated with each other. These results indicate that bacterial nitroreductase plays an important role in forming the DNA adducts, and that the higher the adduct level the higher the level of mutagenicity

Role of unbalanced growth of Gram-negative bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug

Nonsteroidal anti-inflammatory drugs (NSAIDs) induced formation of intestinal ulcers as side effects, in which an unbalanced increase in the number of Gram-negative bacteria in the small intestine plays an important role. To clarify how intestinal microflora are influenced by NSAIDs, we examined the effects of 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), an NSAID, on intestinal motility and on the growth of Escherichia coli and Lactobacillus acidophilus. Transit index, a marker of peristalsis, was not different in BFMeT-treated and solvent-treated rats, indicating that BFMeT increased the number of Gram-negative bacteria without suppression of peristalsis. The factors that affect the growth of intestinal bacteria were not found in intestinal contents of BFMeT-treated rats, because the growth of E. coli and that of L. acidophilus in the supernatants of small intestinal contents of BFMeT-treated rats and solvent-treated rats were not different. The mechanism of the increase in the number of Gram-negative bacteria is still unclear, but heat-killed E. coli cells and their purified lipopolysaccharide (LPS) caused deterioration of BFMeT-induced ileal ulcers, while they could not cause the ulcers by themselves without the NSAID. Concentration of LPS and myeloperoxidase activity level were elevated correlatively in the intestinal mucosa of rats treated with LPS and BFMeT. These results suggest that an increase in the number of Gramnegative bacteria and their LPS in the mucosa induces activation of neutrophils together with the help of NSAID action and causes ulcer formation

PCR-dot blot hybridization based on the neuraminidase-encoding gene is useful for detection of Bacteroides fragilis

Bacteroides fragilis is a Gram-negative obligate anaerobe frequently isolated from clinical specimens and sometimes causes severe septicemia in compromised hosts. Increasing interest has been shown in the enterotoxigenicity and drug resistance of B. fragilis in the field of medical microbiology. We previously reported rapid detection of this anaerobe by nested PCR targeting a neuraminidase-encoding gene nanH. In the present study, we synthesized a digoxigenin-labeled oligonucleotide probe, NH1,which is specific for nanH of B. fragilis, and we combined the hybridization assay using NH1with the nanH-PCR to detect this anaerobe in a bacteremia model mice. In the specificity test, the oligonucleotide probe, NH1, hybridized only to amplification products from B. fragilis. PCR-dot blot hybridization based on nanH enabled detection of cells of B. fragilis in blood samples even when the number was as low as 2x103colony-forming units/ml. These findings suggest that PCR-dot blot hybridization targeting nanH is a useful procedure for diagnosis of septicemia caused by B. fragilis when viable cells in blood cannot be detected by the traditional culture techniques

Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients

<p>Abstract</p> <p>Background</p> <p>Germline mono-allelic promoter hypermethylation of the <it>MLH1 </it>or <it>MSH2 </it>gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene <it>CDH1 </it>(<it>E-cadherin</it>) might cause predisposition to gastric cancer.</p> <p>Methods</p> <p>We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the <it>CDH1 </it>promoter by bisulfite sequencing of multiple clones.</p> <p>Results</p> <p>Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.</p> <p>Conclusion</p> <p>These results suggest that germline mono-allelic hypermethylation of the <it>CDH1 </it>promoter is not a major predisposing factor for gastric cancer.</p