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Darier's disease (DD) is an autosomal dominant genetic disorder caused by mutations in the I ATP2A2 i gene which encodes a sarco/endoplasmic reticulum Ca SP 2+ sp ATPase type 2 isoform (SERCA2).[1] SERCA2 is expressed in epidermal keratinocytes in the skin and neurocytes in the brain. Various psychiatric disorders including schizophrenia have been described in DD patients.[[2], [4]] Thus, although no DD case complicated with ADHD has been reported to date, we assume that her ADHD might be associated with the I ATP2A2 i mutation causative of DD. [Extracted from the article]

Summary: Background: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. Aim: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. Methods: A single‐arm, open‐label, multicentre, intrapatient dose‐escalation, phase 2 study with 4 phases: screening, 3‐month SC (subcutaneous), 3‐month IM (intramuscular) and 6‐month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3‐month SC phase. A ≥50% response rate was considered clinically relevant. Results: Forty‐three patients with late dumping were enrolled; 33 completed the 3‐month SC phase and 23 completed the 12‐month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%‐75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0‐12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). Conclusion: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. [ABSTRACT FROM AUTHOR]

Summary: Objective: Previous work has shown that high body mass index (BMI) is associated with low grey matter volume. However, evidence on the relationship between waist circumference (WC) and brain volume is relatively scarce. Moreover, the influence of mild obesity (as indexed by WC and BMI) on brain volume remains unclear. This study explored the relationships between WC and BMI and grey matter volume in a large sample of Japanese adults. Methods: The participants were 792 community‐dwelling adults (523 men and 269 women). Brain magnetic resonance images were collected, and the correlation between WC or BMI and global grey matter volume were analysed. The relationships between WC or BMI and regional grey matter volume were also investigated using voxel‐based morphometry. Results: Global grey matter volume was not correlated with WC or BMI. Voxel‐based morphometry analysis revealed significant negative correlations between both WC and BMI and regional grey matter volume. The areas correlated with each index were more widespread in men than in women. In women, the total area of the regions significantly correlated with WC was slightly greater than that of the regions significantly correlated with BMI. Conclusions: Results show that both WC and BMI were inversely related to regional grey matter volume, even in Japanese adults with somewhat mild obesity. Especially in populations with less obesity, such as the female participants in current study, WC may be more sensitive than BMI as a marker of grey matter volume differences associated with obesity. [ABSTRACT FROM AUTHOR]

We analyzed 3 hematopoietic stem cell transplant ( HSCT) recipients with inherited chromosomally integrated human herpesvirus-6 (inherited CIHHV-6). Cases 1 (inherited CIHHV-6A) and 2 (inherited CIHHV-6B) were inherited CIHHV-6 recipients. Case 3 received bone marrow from a donor with inherited CIHHV-6B. Following HSCT, HHV-6B was isolated from Case 1. HHV-6A and -6B messenger RNAs were detected in Cases 1 and 3. [ABSTRACT FROM AUTHOR]

Background and Purpose: Histamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin.Experimental Approach: The expression of histamine receptors in pancreatic beta cells was examined by RT-PCR, Western blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H₃ receptors in glucose-induced insulin secretion (GIIS) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H₃ receptors in MIN6 cell proliferation were examined using pharmacological assay and Western blotting.Key Results: Histamine H₃ receptors were expressed in pancreatic beta cells. A selective H₃ receptor agonist, imetit, and a selective inverse H₃ receptor agonist, JNJ-5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ-5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl, indicating that GIIS signalling was affected by H3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element-binding protein (CREB), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H₃ receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation.Conclusions and Implications: Histamine H₃ receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation. [ABSTRACT FROM AUTHOR]

Background and Purpose Histamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin. Experimental Approach The expression of histamine receptors in pancreatic beta cells was examined by RT- PCR, Western blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H3 receptors in glucose-induced insulin secretion ( GIIS) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H3 receptors in MIN6 cell proliferation were examined using pharmacological assay and Western blotting. Key Results Histamine H3 receptors were expressed in pancreatic beta cells. A selective H3 receptor agonist, imetit, and a selective inverse H3 receptor agonist, JNJ-5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ-5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl, indicating that GIIS signalling was affected by H3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element-binding protein ( CREB), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H3 receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation. Conclusions and Implications Histamine H3 receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 1036-1042 (2012) Abstract Aims Serum androgen concentration is reported to be low in patients with Type 2 diabetes. There have been no studies comparing andropausal symptoms such as sleep disturbance, depression, erectile dysfunction and lower urinary tract symptoms simultaneously between men with Type 2 diabetes and subjects without diabetes. Methods We compared andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score in 296 men with Type 2 diabetes and in 267 subjects without diabetes. Furthermore, we evaluated relationships of andropausal symptom scores to various anthropometric factors and compared andropausal symptom scores according to diabetic complications in men with Type 2 diabetes. Results Andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score were 4.2 ± 2.6 vs. 5.0 ± 3.3, P < 0.01 by unpaired Student's t-test, 34.8 ± 8.2 vs. 38.4 ± 9.3, P < 0.0001, 11.5 ± 6.4 vs. 9.9 ± 6.9, P < 0.01 and 7.3 ± 6.7 vs. 9.0 ± 7.1, P < 0.01 in subjects without diabetes and in patients with diabetes, respectively. The Pittsburgh Sleep Quality Index was higher in patients with neuropathy than without. The Self-Rating Depression Scale was higher in patients with advanced retinopathy. The International Index of Erectile Function was lower in patients with advanced retinopathy and nephropathy. The International Index of Erectile Function was lower and the International Prostate Symptom Score was higher in patients with cardiovascular disease than without. Conclusions Our data demonstrated that men with Type 2 diabetes have higher prevalence of andropausal symptoms, especially those with diabetic complications. [ABSTRACT FROM AUTHOR]

Pre-dispersal seed predation by granivorous birds has potential to limit fruit removal and subsequent seed dispersal by legitimate avian seed dispersers in bird-dispersed plants, especially when the birds form flocks. We monitored pre-dispersal seed predation by the Japanese grosbeak, Eophona personata, of two bird-dispersed hackberry species (Cannabaceae), Celtis biondii (four trees) and Celtis sinensis (10 trees), for 3 years (2005, 2007 and 2008) in a fragmented forest in temperate Japan. Throughout the 3 years, predation was more intense on C. biondii, which, as a consequence, lost a larger part of its fruit crop. Grosbeaks preferred C. biondii seeds that had a comparatively lower energy content and lower hardness than C. sinensis, suggesting an association between seed hardness and selective foraging by grosbeaks. In C. biondii, intensive predation markedly reduced fruit duration and strongly limited fruit removal by seed dispersers, especially in 2007 and 2008. In C. sinensis, seed dispersers consumed fruits throughout the fruiting seasons in all 3 years. In C. biondii, variation in the timing of grosbeak migration among years was associated with annual variation in this bird's effects on fruit removal. Our results demonstrate that seed predation by flocks of granivorous birds can dramatically disrupt seed dispersal in fleshy-fruited plants and suggest the importance of understanding their flocking behaviour. [ABSTRACT FROM AUTHOR]

Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants ( HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 ± 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 ± 0.18, P = 0.0011) or day 3 (0.63 ± 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen ( HLA)-mismatched donor was at significant risk for rotavirus antigenemia ( P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT. [ABSTRACT FROM AUTHOR]

The glutamate system including N-methyl-d-aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene ( GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers ( n = 89) than in those with homozygous long alleles ( n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4·11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV. [ABSTRACT FROM AUTHOR]

Background: Increased arterial stiffness is a well-established cardiovascular risk factor. Mechanical stimuli to artery, such as compression, elicit vasodilation and acutely decrease arterial stiffness. As whole-body vibration (WBV)-induced oscillation is propagated at least to lumbar spine, WBV mechanically stimulates abdominal and leg arteries and may decrease arterial stiffness. WBV is feasible in vulnerable and immobilized humans. Therefore, it is worthwhile to explore the possibility of WBV as a valuable adjunct to exercise training. Aim: The aim of this study was to investigate the acute effects of WBV on arterial stiffness. Methods: Ten healthy men performed WBV and control (CON) trials on separate days. The WBV session consisted of 10 sets of vibration (frequency, 26 Hz) for 60 s with an inter-set rest period of 60 s. Subjects maintained a static squat position with knees bent on a platform. In the CON trial, WBV stimulation was not imposed. Blood pressure, heart rate and brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, were measured before and 20, 40 and 60 min after both trials. Results and conclusion: Heart rate and blood pressure did not change from baseline after both trials. Although baPWV did not change in the CON trial (baseline vs. after 20, 40 and 60 min; 1144 ± 35 vs. 1164 ± 41, 1142 ± 39, and 1148 ± 34 cm s−1), baPWV decreased 20 and 40 min after the WBV trial and recovered to baseline 60 min after the trial (1137 ± 28 vs. 1107 ± 30, 1108 ± 28, and 1128 ± 25 cm s−1). These results suggest that WBV acutely decreases arterial stiffness. [ABSTRACT FROM AUTHOR]

Background and Objective: Conventional selective media have been used for the selection of Aggregatibacter (Actinobacillus) actinomycetemcomitans in clinical samples. The proportion of A. actinomycetemcomitans grown on the selective media in vitro may not reflect the true counts in vivo because of the low selectivity. A novel selective medium, designated AASM, was developed for the isolation of A. actinomycetemcomitans. Material and Methods: AASM was prepared by adding of 200 microg/mL of vancomycin and 10 U/mL of bacitracin to AAGM, which contains dextrose, sodium bicarbonate, trypticase soy, yeast extract and agar. Clinical efficacy was evaluated by the recovery, on AASM, of A. actinomycetemcomitans from subgingival samples of 44 periodontally healthy subjects and 76 patients with chronic periodontitis. Results: All serotypes (a-f) of A. actinomycetemcomitans strains grew well, and the average growth recovery of A. actinomycetemcomitans on AASM medium was 94.4% (80.0-109.7%) of that on AAGM. The exclusive rate of other bacteria was 99.9% in clinical samples cultured on AASM. A. actinomycetemcomitans was not detected in periodontally healthy persons but was detected in 25 (32.9%) patients with chronic periodontitis. The predominant serotype was c, detected in 11 subjects. Conclusion: The new selective medium, AASM, was highly selective for A. actinomycetemcomitans, eliminated possible false-positive results and was useful for the isolation of A. actinomycetemcomitans from clinical samples. [ABSTRACT FROM AUTHOR]

Background and Purpose: Protein transduction domains (PTDs), such as Tat, antennapedia homeoprotein (Antp), Rev and VP22, have been extensively utilized for intracellular delivery of biologically active macromolecules in vitro and in vivo. There is little known, however, about the relative transduction efficacy, cytotoxicity and internalization mechanism of individual PTDs.Experimental Approach: We examined the cargo delivery efficacies of four major PTDs (Tat, Antp, Rev and VP22) and evaluated their toxicities and cell internalizing pathways in various cell lines.Key Results: The relative order of the transduction efficacy of these PTDs conjugated to fluorescein was Rev>Antp>Tat>VP22, independent of cell type (HeLa, HaCaT, A431, Jurkat, MOLT-4 and HL60 cells). Antp produced significant toxicity in HeLa and Jurkat cells, and Rev produced significant toxicity in Jurkat cells. Flow cytometric analysis demonstrated that the uptake of PTD-fluorescein conjugate was dose-dependently inhibited by methyl-beta-cyclodextrin, cytochalasin D and amiloride, indicating that all four PTDs were internalized by the macropinocytotic pathway. Accordingly, in cells co-treated with 'Tat-fused' endosome-disruptive HA2 peptides (HA2-Tat) and independent PTD-fluorescent protein conjugates, fluorescence spread throughout the cytosol, indicating that all four PTDs were internalized into the same vesicles as Tat.Conclusions and Implications: These findings suggest that macropinocytosis-dependent internalization is a crucial step in PTD-mediated molecular transduction. From the viewpoint of developing effective and safe protein transduction technology, although Tat was the most versatile carrier among the peptides studied, PTDs should be selected based on their individual characteristics. [ABSTRACT FROM AUTHOR]

We investigated killer cell immunoglobulin-like receptor ( KIR) genotypes in 92 patients with young-onset type 1 diabetes mellitus (YT1DM: ≤35 years old), 112 patients with adult-onset type 1 diabetes mellitus (AT1DM: >35 years old) and 240 control subjects. There were no differences in the frequency of KIR genotypes between controls and all the patients with T1DM or patients grouped according to age at onset of the disorder. However, when the subjects were classified into three groups according to combinations of the presence or absence of KIR3DS1/ KIR3DL1 and its ligand human leukocyte antigen (HLA)-Bw4, or KIR2DL1 and its ligand HLA-C group 2, the genotype distribution was significantly different between the patients with AT1DM and controls [ χ2= 5.993, 2 degrees of freedom (d.f.), P= 0.0500]. These data suggest that KIR polymorphisms may be associated with the age at onset of T1DM. [ABSTRACT FROM AUTHOR]

Background Increase in interleukin-8 in the oesophageal mucosa has been associated with the pathogenesis of reflux oesophagitis. Aim To assess the effect of bile acids on the interleukin-8 expression in normal human oesophageal epithelial cells and to determine its molecular mechanisms. Methods Human oesophageal epithelial cells were stimulated with unconjugated bile acids, conjugated bile acids and inflammatory cytokines. Protein and mRNA of interleukin-8 were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. In addition, we examined protein kinases and transcription factors involved in interleukin-8 synthetic pathways using protein kinase inhibitors and luciferase expression vectors, respectively. Results Unconjugated bile acids induced interleukin-8 production from human oesophageal epithelial cells stronger than conjugated bile acids. However, conjugated bile acids in acidic media resulted in remarkable increase of interleukin-8 production compared with those in neutral-pH media. Mutation of the binding site of NF-kB, AP-1 and NF-IL6 abrogated the induction of luciferase activities by 100%, 70% and 30%, respectively. Inhibitor of protein kinase A, protein kinase C or p38 mitogen-activated protein kinase attenuated the production of interleukin-8 by cholic acid. Conclusions These results indicate that bile acids induce interleukin-8 expression from oesophageal epithelial cells mainly via the activation of NF-kB as well as AP-1. [ABSTRACT FROM AUTHOR]

Background Recent studies in models of inflammatory bowel disease have demonstrated that heme oxygenase-1 (HO-1) induction, or its by-products in this process such as carbon monoxide (CO), plays an important role in the intestinal inflammation. However, the distribution of HO-1 in intestinal mucosa and the concentration of intestinal luminal CO in humans have not yet been investigated. Aim To detect the HO-immunopositive cells in the intestine of normal subjects and in patients with ulcerative colitis (UC) and to measure intestinal luminal CO gas contents using gas chromatography. Materials and Methods The expression of HO-1 in the intestine was determined using immunohistochemistry. Human colonic gas was collected using colonoscopy from healthy volunteers and patients with UC. Analysis of intestinal luminal gas was performed using a newly developed portable gas chromatograph. Results Immunopositive staining for HO-1 was localized in the inflammatory cells, mainly mononuclear cells, and the number of cells that accepted stain was greater in patients with UC. CO level in the intestinal lumen significantly increased in patients in the active stage of UC. Conclusion These findings indicate that the HO-CO system is induced in UC. [ABSTRACT FROM AUTHOR]

A number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases. Tryptase is one of the serine proteases that stored almost exclusively in the secretory granules of mast cells. It acts to induce microvascular leakage, the chemotaxis of inflammatory cells, and stimulates the release of inflammatory cytokines through the mitogen-activated protein kinase /activator protein-1 pathway and protease-activated receptor (PAR) nuclear factor- κB pathway. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. The effect of anti-tryptase therapy on human inflammatory bowel disease and experimental colitis has been demonstrated. The result of a pilot study has revealed that systemic administration of a specific tryptase inhibitor is safe and there is evidence of activity in the treatment of ulcerative colitis. Recently, we found that nafamostat mesilate, which selectively inhibits tryptase activity at low concentration, could reduce intestinal inflammation in rats. In addition, nafamostat mesilate enema improved clinical and endoscopic findings in ulcerative colitis patients, resistant to conventional therapy such as corticosteroids and sulfasalazine/5-aminosalicylic acid. These studies suggest that anti-tryptase therapy may represent a new therapeutic strategy for human inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora. Aim To reveal the distinct gene expression clusters of a lipopolysaccharide-stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease. Materials and methods Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high-density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center. Results Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease. Conclusion We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients. [ABSTRACT FROM AUTHOR]

It is well known that one drawback for stress-ribbon bridges can be that significant horizontal reactions at the abutment can be generated and that they have low flexural stiffness. The latter prevents them from being used as roadway bridges. A new hybrid structure of stress-ribbon deck and truss has been proposed and was adopted in the construction of Nozomi Bridge in Japan, a roadway bridge opened to traffic in 2003. Static and dynamic behaviours of the hybrid structure have been studied analytically and experimentally. The results show that the hybrid bridge has advantages over the stress-ribbon deck bridge as it generates much less horizontal force in suspension cables and has higher flexural stiffness, suitable for use as a roadway bridge, and that the hybrid bridge has advantages over the truss bridge since it can be constructed without extensive falsework and without large erection equipment. In this paper, at first, the hybrid structure is described, then analytical and test results are used to show its static and dynamic characteristics, and finally the construction of Nozomi Bridge is outlined. [ABSTRACT FROM AUTHOR]

Background Diesel exhaust particles (DEP) can enhance various respiratory diseases. However, it is unclear as to which components in DEP are associated with the enhancement. We investigated the effects of DEP components on antigen-related airway inflammation, using residual carbonaceous nuclei of DEP after extraction (washed DEP), extracted organic chemicals (OC) in DEP (DEP–OC), and DEP–OC plus washed DEP (whole DEP) in the presence or absence of ovalbumin (OVA). Methods Male ICR mice were intratracheally administrated with OVA and/or DEP components. We examined the cellular profile of bronchoalveolar lavage (BAL) fluid, histological changes, lung expression of inflammatory molecules, and antigen-specific production of IgG1 in the serum. Results DEP–OC, rather than washed DEP, enhanced infiltration of inflammatory cells into BAL fluid, magnitude of airway inflammation, and proliferation of goblet cells in the airway epithelium in the presence of OVA, which was paralleled by the enhanced lung expression of eotaxin and IL-5 as well as the elevated concentration of OVA-specific IgG1. In contrast, washed DEP with OVA showed less change and increased the lung expression of IFN-γ. The combination of whole DEP and OVA caused the most remarkable changes in the entire enhancement, which was also accompanied by the enhanced expression of IL-13 and macrophage inflammatory protein-1α. Conclusion DEP–OC, rather than washed DEP, exaggerated allergic airway inflammation through the enhancement of T-helper type 2 responses. The coexistence of OC with carbonaceous nuclei caused the most remarkable aggravation. DEP components might diversely affect various types of respiratory diseases, while whole DEP might mostly aggravate respiratory diseases. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with Type 2 diabetes. Both light-to-moderate alcohol consumption and higher serum concentrations of dehydroepiandrosterone (DHEA) are associated with reduced CVD mortality, raising the possibility of DHEA as a causal intermediate in CVD and alcohol consumption. Methods Relationships between alcohol consumption and serum DHEA sulphate (DHEA-S) concentration, carotid atherosclerosis as evaluated by carotid ultrasonography and major cardiovascular risk factors were investigated in 404 consecutive men with Type 2 diabetes. Patients were divided into three groups according to mean ethanol consumption per week: non-drinkers, light-to-moderate drinkers (< 210 g per week) or heavy drinkers (≥ 210 g per week). Results Plasma HDL-cholesterol was positively associated with the degree of alcohol consumption. Intima-media thickness (0.92 ± 0.21 vs. 1.09 ± 0.35 mm, P < 0.0001) and plaque score (3.0 ± 3.3 vs. 5.2 ± 4.9, P = 0.008) were lower in light-to-moderate drinkers than in non-drinkers. Serum DHEA-S concentrations were higher in light-to-moderate drinkers (1264.2 ± 592.2 ng/ml, P < 0.0001) and heavy drinkers (1176.2 ± 607.6 ng/ml, P = 0.0100) than in non-drinkers (956.8 ± 538.6 ng/ml). In a subgroup aged 60–75-year-old patients ( n = 277), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1126.8 ± 502.5 ng/ml, P = 0.0121) than in non-drinkers (937.9 ± 505.1 ng/ml). Also, in a subgroup without CVD ( n = 339), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1328.5 ± 593.7 ng/ml, P < 0.0001) than in non-drinkers (970.1 ± 540.7 ng/ml). Conclusions Higher serum DHEA-S concentrations in light-to-moderate drinkers may represent part of the link between light-to-moderate alcohol consumption and lower CVD mortality. [ABSTRACT FROM AUTHOR]

Adults aged 65 and over comprise the fastest growing segment of the U.S. population, and older adults experience greater morbidity and mortality due to infection than young adults. While this factor is well established, most clinical investigation of infectious diseases in the aged focuses on microbiology, and crude endpoints of clinical success such as cure rates or mortality, but often fails to assess functional status, a critical variable in geriatric care. Functional status can be evaluated as a risk factor for infectious disease or an outcome of interest following specific interventions utilizing well-validated instruments. This paper outlines the currently available data suggesting a link between infection, immunity and impaired functional status in the elderly, summarizes commonly employed instruments used to determine specific aspects of functional status, and provides recommendations for a new paradigm in which clinical trials of older adults include functional assessment. [ABSTRACT FROM AUTHOR]

Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). Three mammalian HO isozymes have been identified, one of which, HO-1, is a stress-responsive protein induced by various oxidative agents. HO-2 and HO-3 genes are constitutively expressed. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to the resolution of inflammation and have protective effects in several organs against oxidative injury. Although the mechanism underlying the anti-inflammatory actions of HO-1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the intestinal tract, HO-1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by trinitrobenzene sulphonic acid or dextran sulphate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the intestinal tract. These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5mg/mouse/day). Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody. [ABSTRACT FROM AUTHOR]

Summary Background : Recent studies have shown that Helicobacter pylori affects intracellular signal transduction in host cells, leading to the activation of transcriptional factors and the induction of pro-inflammatory cytokines. On the other hand, rebamipide, an anti-gastritis and anti-ulcer agent, could scavenge reactive oxygen species and reduce interleukin-8 (IL-8) expression in gastric epithelial cells induced by H. pylori -stimulation through the attenuated activation of nuclear factor-κB (NF-κB). Aims : In this study, we investigated the effects of rebamipide on gene expression in H. pylori -stimulated epithelial cells using DNA chip. Methods : H. pylori water extract (HPE) was prepared from NCTC11637, the type strain of H. pylori . Total RNA was extracted from MKN45 cells, a human gastric cancer cell line, following HPE-stimulation with and without rebamipide for 3 h, and differences in gene expression profiles were observed using GeneChip and Human 6800 probe array. Results : The GeneChip analysis demonstrated that 132 up-regulated genes and 873 down-regulated genes, such as growth factors, chemokines and transcription factors, were detected in MKN45 cells 3 h after stimulation of H. pylori . Among them, several genes, including bFGF, RANTES and MIP-2β, were previously unknown to be expressed in H. pylori -stimulated human gastric cells. Rebamipide reduced expression of 119 genes encoding cytokines, growth factors and their receptors and transcription factors. Conclusions : These findings suggest that rebamipide could inhibit inflammatory reactions and tumour progression by modifying H. pylori infection-induced gene expression in gastric epithelial cells. [ABSTRACT FROM AUTHOR]

Summary Aims : To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro-mucosal inflammation after eradication. Methods : Two hundred and six H. pylori -positive patients with active gastric ulcer underwent 8-week based therapy (OA) consisting of 2-week amoxicillin with omeprazole and subsequent 6-week omeprazole. They randomly received either rebamipide (OA-R) or placebo (OA-P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically. Results : Per Protocol Set analysis showed no significant difference in eradication rate between OA-R (64.6%; 95% confidence interval, 54.3–75.0%) and OA-P (67.9%; 95% CI, 57.6–78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA-R (1.84 ± 0.41) compared with that in OA-P (2.02 ± 0.39) after 16-weeks of treatment. This suppressive effect on inflammation was observed even in the OA-R patients unsuccessfully eradicated. Conclusion : Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate. [ABSTRACT FROM AUTHOR]

Summary A mass developed in the mandibular gingiva of a thoroughbred racehorse. When the horse could no longer eat unassisted, it was killed and immediately autopsied. Macroscopically, the mandible exhibited extensive osteolysis, with only a small amount of bone remaining around the tooth roots. The cut surface of the mass around the mandible consisted of neoplastic medullary tissue, in which osteogenesis was observed. The medullary tissue was composed of pleomorphic medium-sized to large cells, interlaced by collagen bundles. These cells had large, pale, round or ovoid, sometimes cleaved nuclei, with one or two prominent nucleoli. Mitoses were numerous. Electron microscopy showed that the cells in the medullary tissues were similar in shape to undifferentiated lymphocytes. Immunohistochemically, these cells were positive for B-cell associated antigen in the pre-B-cell stage. Our findings suggest that the horse had extranodal lymphoblastic lymphoma of suspected B-cell lineage, possibly originating from the lymphatic system of the gingiva. We consider that the osteolysis resulted from activation of osteoclasts by proliferation of the tumour cells. [ABSTRACT FROM AUTHOR]

Abstract: Human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) are ubiquitous in the human population and cause exanthem subitum, a benign disease seen in infancy. The viruses remain latent in the body after primary infection, and reactivate in immunocompromised patients. HHV-6 infection occurs in nearly 50% of all bone marrow and in 20–30% of solid-organ transplant recipients, 2–3 weeks following the procedure. It has been suggested that the viral infection and activation result in clinical symptoms, including fever, skin rash, pneumonia, bone marrow suppression, encephalitis, and rejection. In order to understand the viral infection in greater detail, several studies investigating the route of viral transmission and diagnostic procedures have been carried out. In contrast to studies of HHV-6 infection in organ-transplant recipients, the number of studies examining HHV-7 infection in these patients is limited. According to several recent studies, HHV-7 may act as a cofactor for cytomegalovirus disease in organ-transplant recipients. [ABSTRACT FROM AUTHOR]

Aims Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. Methods We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. Results The frequency of ICAM-1 469KK( genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, X² = 6.70, P = 0.035; allele 66% vs. 50%, X² = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51fold increased risk for retinopathy. Conclusions These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis factor (TNF-α) is a candidate factor for involvement in inflammation-mediated gastric mucosal injury. However, the effect of this cytokine on gastric epithelial cells has been poorly investigated. In the present study, we examined whether gastric epithelial cells are resistant to TNF- α-induced apoptosis, and whether this resistance is related to ubiquitin-proteasome-associated nuclear factor-κB (NF-κB) activation. Methods: The rat gastric mucosal cell line RGM-1 was grown in DMEM/F12 medium supplemented with 10% FCS. Confluent monolayers of cells were pretreated or not for 60 min with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin-like activity of 26S proteasome. Cells were subsequently stimulated with recombinant rat TNF-α and their viability was determined by WST-1 assay. Apoptosis was confirmed by fluorescence microscopy after staining with Hoechst 33342 and propidium iodide, and DNA fragmentation was determined by flow cytometry using an APO-BRDU kit. IκB-α and the p65 binding subunit of NF-κB were detected by Western blots. Results: Twenty-four-hour incubation with TNF-α alone or PSI alone did not affect the cell viability of RGM-1 cells. Pretreatment with PSI significantly enhanced the level of apoptosis induced by TNF-α. In RGM-1 cells treated with TNF-α, cytoplasmic IκB-α decreased and p65 in nuclear extracts increased markedly 30 min after cytokine stimulation. Pretreatment with PSI at 12.5 μmol/L blocked these TNF-α-induced changes. Conclusion: PSI enhances TNF-α-induced apoptosis through inhibition of NF-κB activation in RGM-1 cells. [ABSTRACT FROM AUTHOR]

Background: H. pylori infection potentiates aspirin-induced gastric mucosal injury by mechanisms that include accumulation of activated neutrophils. Aim: To determine the role of elastase and active oxygen species (AOS) produced by activated neutrophils in the gastric mucosal injury induced by administration of acidified aspirin to H. pylori -infected Mongolian gerbils. Methods: H. pylori ATCC43504 culture broth was administered by oral gavage to male Mongolian gerbils at 7 weeks of age. After 4 weeks, acidified aspirin (400 mg/kg) was administered orally, and 3 h later, the total area of gastric erosions, myeloperoxidase (MPO) activity (an index of neutrophil accumulation), thiobarbituric acid-reactive substances (TBARS, an index of lipid peroxidation), and KC/GRO (a chemo-attractive cytokine in rodents) were measured in gastric mucosa. To determine the role of elastase or AOS derived from neutrophils in these circumstances, ONO-5046 (an elastase inhibitor), a combination of superoxide dismutase (SOD) and catalase (scavengers of AOS), and polaprezinc (an anti-ulcer agent with anti-inflammatory effects) were administered before aspirin. Results: ONO-5046 inhibited the increase in gastric erosions and mucosal TBARS induced by administration of aspirin to H. pylori -infected gerbils, but not the increases in MPO activity or KC/GRO contents. A combination of SOD and catalase or polaprezinc significantly reduced gastric erosions, TBARS concentrations, MPO activity and KC/GRO concentration. Conclusions: These results suggest that neutrophil-derived-elastase and -oxidants play an important role in the gastric mucosal injury induced by administration of aspirin to H. pylori -infected gerbils. [ABSTRACT FROM AUTHOR]

Background: Neutrophils activation and tumour necrosis factor-α (TNF-α) induction play a critical role in aspirin-induced gastric mucosal injury. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-γ ligand, can ameliorate aspirin-induced gastric mucosal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-α expression. Methods: Aspirin-induced injury was produced by the intragastric administration of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 mL/kg). Pioglitazone was given to the rats by gastric intubation 1 h before the aspirin administration. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The gastric concentration of TNF-α and the expression of TNF-α mRNA was determined by ELISA and reverse transcriptase-polymerase chain reaction. Results: The intragastric administration of acidified aspirin induced hyperemia and haemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by treatment with pioglitazone in a dose-dependent manner. The increases in thiobarbituric acid-reactive substances and myeloperoxidase activity after aspirin administration were both significantly inhibited by pre-treatment with pioglitazone (10 mg/kg). The gastric content of TNF-α increased and the expression of TNF-α mRNA was up-regulated after aspirin treatment. However, the peak TNF-α mRNA expression 1 h after aspirin administration was inhibited by pioglitazone. Conclusion: Based on these data, the beneficial effects of pioglitazone on... [ABSTRACT FROM AUTHOR]

Summary: Atrophy of seminiferous tubules and interstitial fibrosis are frequently observed in aged horses. Samples from 8 male Thoroughbreds, age 4–24 years, were subjected to histological, electron microscopical and immunohistochemical examination and statistical analysis. There were statistically significant increases in collagen fibres in the lamina propria of seminiferous tubules and testicular interstitium in 3 horses age 23 and 24 years compared with 5 horses age 4–20 years (P<0.001). Lamina propria surrounding atrophic tubules was thickened by an increase in collagen type IV and elastic fibres and by proliferation of bizarre myoid cells. Basal lamina was also thickened but had decreased reactivity for collagen type IV. Some myoid cells changed morphologically to a swollen and irregular shape and contained abundant cytoplasmic organelles. Laser scanning microscopy revealed that cytoplasmic actin filaments were decreased; the remaining filaments were positive for α‐smooth muscle actin and vimentin, and matrix metalloproteinase‐2 was secreted. These myoid cells transformed into myofibroblasts. The changes are interpreted as evidence of injured structure and function of the lamina propria and basal lamina and may explain the functional decline of the blood‐testis barrier. Myoid cells may play an important role in the progression of testicular fibrosis. [ABSTRACT FROM AUTHOR]

Abstract. Leukocyte-endothelial cell interactions, which are mediated by various adhesion molecules, are a crucial event in inflammatory reactions including atherosclerosis. alpha-Tocopherol (alpha-Toc) has been used for protection and therapy of vascular diseases because of its antioxidant activity. The objective of the present study was to determine effect of alpha-Toc on endothelial-dependent adhesive interactions with leukocytes elicited by oxidized low density lipoprotein (oxLDL). Incubation of HUVEC with oxLDL (100 micro g/mL) increased expression of proteins and messenger RNA of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on enzyme immunoassay and northern blotting assay; pretreatment with alpha-Toc reduced in a dose dependent manner. Adherence of polymorphonuclear leukocytes (PMN) or mononuclear leukocytes (MNC) to oxLDL-activated HUVEC was much increased compared with that to unstimulated HUVEC. Treatment of HUVEC with alpha-Toc, monoclonal antibody to ICAM-1 or VCAM-1 inhibited adherence of PMN or MNC in a dose dependent manner. These results suggest that alpha-Toc works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with leukocytes induced by oxLDL. [ABSTRACT FROM AUTHOR]

Nitric oxide synthase activity is increased in the stomach in association wit Helicobacter pylori infection and portal hypertension, but the mechanism by which nitric oxide contributes to mucosal damage remains unclear. To examine whether nitric oxide injures gastric mucosal cells and whether cellular glutathione affects nitric oxide-induced cytotoxicity. Excess exogenous nitric oxide produced by NOC5 or NOC12 induced necrosis in RGM-1 cells in a time- and concentration-dependent manner. The level of reduced glutathione drastically decreased prior to the loss of cell viability and remained low, but oxidized glutathione was not affected. Glutathione depletion increase necrosis of both NOCs in an NOC-concentration-related fashion, while pre-treatment with γ-glutamylcystein ethyl ester reduced their necrotic susceptibility. Exogenous nitric oxide induced necrosis in gastric mucosal cells, and intracellular reduced glutathione protects gastric mucosal cells from damage by nitric oxide. [ABSTRACT FROM AUTHOR]

Neutrophil—endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal inflammation associated with Helicobacter pylori or nonsteroidal anti­inflammatory drugs. To investigate the effects of proton pump inhibitors and histamine­2 receptor antagonists (HRA) on neutrophil­endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin­1β (IL­1β). Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibttors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Nentrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule­1 (ICAM­1) and vascular adhesion molecule­1 (VCAM­1) were assessed by flow cytometry and an enzyme lmmunoassay. respectively. Neutrophil adherence was defined as the ratio of exogenous neutrophils that adhered to the endothelial monolayers. The expression of CD11b and CDI8 on neutrophils and neutrophil­dependent adhesion to endothelial cells elicited by HPE were inhibited by lansoprazole and omeprazole at clinical relevant doses, and the expression of ICAM­1 and VCAM­1 on endothelial cells and endothelial­dependent neutrophil adherence induced by IL­1β were also inhibited by lansoprazole and omeprasole at similar doses. Famotidine and ranitidine had no effect on neutrophil—endothelial cell interactions. These results Indicate that proton pump inhibitors can attenuate neutrophil adherence to endothelial cells via inhibiting the expression of adhesion molecules, suggesting that proton pump inhibitors may have anti­inflammatory activity. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to 1) determine the time-course of T-lymphocyte adhesion to monolayers of human umbilical vein endothelial cell (HUVEC) that were exposed to 60 min of anoxia followed by 24 h of reoxygenation, and 2) define the mechanisms responsible for the hyperadhesivity of post-anoxic HUVEC to human T-lymphocytes. Methods: Human peripheral blood mononuclear leukocytes were isolated from heparinized peripheral blood. T-lymphocytes were obtained by negative selection using a MACS column. HUVEC monolayers were exposed to anoxia/ reoxygenation (A/R), and then reacted with [SUP51]Cr -labeled T-lymphocytes in adhesion assays. Results: A/R leads to an increased adhesion of T-lymphocytes to HUVEC monolayers, with peak responses occurring at 8 h after reoxygenation. This adhesion response was largely attributed to the CD4[SUP+] T-cell subset. The hyperadhesivity of A/R-exposed HUVEC was inhibited by monoclonal antibodies directed against either LFA-1, VLA-4, ICAM-1, or VCAM-1, indicating a contribution of these adhesion molecules and their ligands. Moreover, T-cell hyperadhesivity was attenuated by anti- IL-8, consistent with a role for this chemokine in the adhesion response. Protein synthesis inhibitors (actinomycin D and cycloheximide) as well as chemical inhibitors of (and binding ds-oligonucleotides to) NFκB and AP-1 significantly attenuated the A/R-induced T-lymphocyte adhesion responses. The kinetics of VCAM-1 on post-anoxic HUVEC correlated with the T-lymphocyte adhesion response. Conclusions: A/R elicits a T-lymphocyte-endothelial cell adhesion response that involves transcription-dependent surface expression of VCAM- 1. [ABSTRACT FROM AUTHOR]

Presents a study on the characteristics of the production of active oxygen species from the neutrophils that have adhered to the endothelial cells, fibronectin or polystyrene. Use of electron paramagnetic resonance spin trapping; Methodology; Results and discussion; Conclusions.

Acute, low-dose ultraviolet B radiation (UVB) impairs the induction of contact hypersensitivity (CH) to dinitrochlorobenzene (DNCB) in certain inbred strains of mice (termed UVB-susceptible), but not in others (termed UVB-resistant). By contrast, exposure of mouse ear skin to an identical regimen of UVB has been reported to exaggerate the expression of CH. Recently, tumour necrosis factor-alpha (TNF-α) has been demonstrated to mediate the deleterious effects of UVB on CH induction, presumably through local release of TNF-α within UVB exposed skin. The present studies were conducted to determine whether TNF-α also mediates the exaggerated expression of CH induced by UVB radiation. It was found that TNF-α, injected intradermally at the ear challenge site, enhanced the expression of CH to DNFB in conventionally sensitized mice. Interestingly, TNF-α was able to amplify the expression of CH in the ears of both UVB-susceptible strains of mice, and UVB-resistant strains. However, anti-TNF-α antibodies neutralized UVB-enhanced CH in UVB-susceptible mice, but not in UVB-resistant mice. These findings support the proposition that TNF-α released from UVB-exposed epidermal cells, is a critical mediator of the effects of UVB radiation on induction and expression of contact hypersensitivity. The effects of UVB radiation, intradermal (ID) TNF-α, and/or epicutaneously applied DNFB on epidermal Langerhans' cells were also evaluated and compared. Whereas epicutaneously applied DNFB alone profoundly depleted the epidermis of Langerhans' cells, DNFB painted on UVB-exposed or TNF-α-treated skin was much less effective at eliminating normal appearing Langerhans' cells. These results suggest that one direct effect of TNF-α on Langerhans' cells may be to immobilize these antigen-presenting cells transiently within the epidermis. It is proposed that this immobilization has the paradoxical effects (a) of interfering with sensitization, by preventing hapten-bearing Langerhans' cells from migrating to the draining lymph node, while at the same time (b) of amplifying CH expression by lengthening the interval of hapten retention and presentation with the epidermis. [ABSTRACT FROM AUTHOR]