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CD4+ T cells not only direct immune responses against infectious micro-organisms but are also involved in the pathogenesis of inflammatory diseases. In the last two to three decades, various researchers have identified and characterized several functional CD4+ T-cell subsets, including T-helper 1 (Th1), Th2, Th9 and Th17 cells and regulatory T (Treg) cells. In this mini-review, we introduce the concept of pathogenic Th cells that induce inflammatory diseases with a model of disease induction by a population of pathogenic Th cells: the ‘pathogenic Th population disease-induction model’. We will focus on Th2 cells that induce allergic airway inflammation—pathogenic Th2 cells (Tpath2 cells)—and discuss the nature of Tpath2 cells that shape the pathology of chronic inflammatory diseases. Various Tpath2-cell subsets have been identified and their unique features are summarized in mouse and human systems. Second, we will discuss how Th cells migrate and are maintained in chronic inflammatory lesions. We propose a model known as the ‘CD69–Myl9 system’. CD69 is a cell surface molecule expressed on activated T cells and interaction with its ligand myosin light chain 9 (Myl9) is required for the induction of inflammatory diseases. Myl9 molecules in the small vessels of inflamed lungs may play a crucial role in the migration of activated T cells into inflammatory lesions. Emerging evidence may provide new insight into the pathogenesis of chronic inflammatory diseases and contribute to the development of new therapeutic strategies for intractable inflammatory disorders.

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection–triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1–expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)–containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d‐positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d‐negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d‐negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d‐independent manner, however still in a TCR‐mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d‐negative leukemia cells (K562, HL‐60, REH) as well as αGalCer‐loaded CD1d‐positive Jurkat cells. The CD1d‐independent cytotoxicity was enhanced by natural killer cell‐activating receptors such as NKG2D, 2B4, DNAM‐1, LFA‐1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d‐negative leukemia cells. In contrast, TCR was essential for CD1d‐independent recognition and cytotoxicity. iNKT cells degranulated toward patient‐derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti–tumor mechanism of iNKT cells in targeting CD1d‐negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d., Activated human iNKT cells directly recognize leukemia cells, especially myeloid malignancies, in a CD1d‐independent manner. The CD1d‐independent cytotoxicity of iNKT cells depends on Vα24Vβ11‐T cell receptor and is enhanced by NK cell‐activating receptors.

application/pdf, Journal of Nutrition, Health and Aging. 2022, 26 (2), P.157-160

CD69 is an activation marker on leukocytes. Early studies showed that the CD69+ cells were detected in the lung of patients with asthmatic and eosinophilic pneumonia, suggesting that CD69 might play crucial roles in the pathogenesis of such inflammatory diseases, rather than simply being an activation marker. Intensive studies using mouse models have since clarified that CD69 is a functional molecule regulating the immune responses. We discovered that Myosin light chain 9, 12a, 12b (Myl9/12) are ligands for CD69 and that platelet-derived Myl9 forms a net-like structure (Myl9 nets) that is strongly detected inside blood vessels in inflamed lung. CD69-expressing activated T cells attached to the Myl9 nets can thereby migrate into the inflamed tissues through a system known as the CD69-Myl9 system. In this review, we summarize the discovery of the CD69-Myl9 system and discuss how this system is important in inflammatory immune responses. In addition, we discuss our recent finding that CD69 controls the exhaustion status of tumor-infiltrating T cells and that the blockade of the CD69 function enhances anti-tumor immunity. Finally, we discuss the possibility of CD69 as a new therapeutic target for patients with intractable inflammatory disorders and tumors.

IntroductionDirect-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.MethodsSeveral design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and disseminationDirect-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration numberClinicalTrials.gov Registry (NCT04358302).

The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create “Myl9 nets” that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.

Drinking water quality for children should be higher than adults due to both behavioral and physiological factors. Thus, to provide enough, safe, and easily accessible drinking water for children at schools, the Shanghai Municipal Government initiated a direct-drinking water project in 2013. However, there has been no study so far to assess the quality of direct-drinking water or to investigate its risk factors in Shanghai elementary and middle schools.In the present study, we selected direct-drinking water equipment from 183 elementary and middle schools (17% of total) in Shanghai to detect the colony-forming units (CFU), residual chlorine, chemical oxygen demand (COD), and turbidity of water samples, and analyzed the risk factors of its quality using both simple and multiple linear regression analysis.Results showed that the CFU, residual chlorine, COD, and turbidity of direct-drinking water in Shanghai elementary and middle schools ranged fromLOD-300 cfu/mL,LOD-0.670 mg/L, 0.090-2.710 mg/L, and 0.100-2.050 NTU, respectively. The results of simple linear regression analysis indicated that the CFU of direct-drinking water significantly increased when water temperature was between 25 and 60 °C (β = 19.862, p = 0.030), but it was decreased at 60-100 °C (β = - 16.387, p = 0.046). Additionally, the CFU was higher in elementary schools than middle schools, which was also affected by faucet type and water treatment technology (p = 0.006, 0.012 and 0.042, respectively). The residual chlorine in direct-drinking water significantly increased when there was no toilet within 10 m (β = 0.012, p = 0.045). The COD of direct-drinking water was significantly higher in rural areas and in warm water, compared to urban areas (p = 0.033) and room temperature water (p = 0.000), respectively. The turbidity of direct-drinking water was significantly higher in urban areas and water using UF/MF technology, compared to rural areas (p = 0.030) and RO technology (p = 0.009), respectively. The results of multiple linear regressions analysis drew the same conclusions.In order to improve the quality of direct-drinking water, the equipment should be as far away from toilet as possible and direct-drinking water should be kept at room temperature or heated at high temperature (over 60 °C). Furthermore, sanitary standards of direct-drinking water quality and relevant laws and regulations should be established and implemented as soon as possible. Our study demonstrates that it is critical to improve direct-drinking water quality and ensure the safety of drinking water in elementary and middle schools in Shanghai.

Lead contamination in the City of Flint, MI has been well documented over the past two years, with lead levels above the EPA Action Level until summer 2016. This resulted from an ill-fated decision to switch from Detroit water (Lake Huron) with corrosion control, to Flint River water without corrosion control. Although lead levels are now closer to normal, reports of skin rashes have sparked questions surrounding tap water in some Flint homes. This study investigated the presence of contaminants, including disinfection by-products (DBPs), in the hot tap water used for showering in the homes of residents in Flint. Extensive quantitative analysis of 61 regulated and priority unregulated DBPs was conducted in Flint hot and cold tap water, along with the analysis of 50 volatile organic compounds and a nontarget comprehensive, broadscreen analysis, to identify a possible source for the reported skin rashes. For comparison, chlorinated hot and cold waters from three other cities were also sampled, including Detroit, which also uses Lake Huron as its source water. Results showed that hot water samples generally contained elevated levels of regulated and priority unregulated DBPs compared to cold water samples, but trihalomethanes were still within regulatory limits. Overall, hot shower water from Flint was similar to waters sampled from the three other cities and did not have unusually high levels of DBPs or other organic chemicals that could be responsible for the skin rashes observed by residents. It is possible that an inorganic chemical or microbial contaminant may be responsible.

Disinfected water is the major source of haloacetic acids (HAAs) in humans, but their inter- and intra-individual variability for exposure and risk assessment applications is under-researched. Thus, we measured HAAs in cross-sectional and longitudinal urine and water specimens from 17 individuals. Five regulated HAAs&mdash, mono, di, and trichloroacetic acid (MCAA, DCAA, and TCAA) and mono- and dibromoacetic acid (MBAA and DBAA)&mdash, and one unregulated HAA&mdash, bromochloroacetic acid (BCAA)&mdash, were measured. Urinary DCAA, MBAA, DBAA, and BCAA levels were always below the limits of detection (LOD). Measured levels and interindividual variability of urinary MCAA were higher than urinary TCAA. Longitudinal urinary specimens showed MCAA levels peaked in after-shower specimens, while TCAA levels remain unchanged. Correlation between urinary MCAA and TCAA was moderate but statistically significant. The prevalence of MCAA and TCAA in urine suggest they can be considered as biomarkers of HAA. Peak urinary MCAA in post-shower specimens suggest MCAA captures short-term exposure via dermal and/or inhalation, while urinary TCAA captures long-term exposure via ingestion. However, further research is warranted in a large pool of participants to test the reliability of MCAA as exposure biomarker.

It is well known that lactic acid bacteria supplementation is beneficial for intestinal conditions such as microbiota; however, the effects of killed-lactic acid bacteria on intestinal conditions are largely unclear. This study aimed to evaluate the effect of heat-killed Lactobacillus kunkeei YB38 (YB38) at a dose of approximately 10 mg/day on human intestinal environment and bowel movement. This single-blind study enrolled 29 female subjects with a low defecation frequency who consumed heat-killed YB38 at four increasing dosage levels: 0 (placebo), 2, 10, and 50 mg. Each dose was consumed daily for two weeks, with a two-week baseline period preceding the dosing-period and a two-week washout period ending the study. Observed levels of Bacteroides fragilis group significantly decreased with intake of heat-killed YB38 at ≥10 mg/day compared with levels during placebo intake (P

Swimming pool disinfection byproducts (DBPs) are becoming increasingly common worldwide. Precise exposure and health risk assessment for DBPs in swimming pool water with optimized parameters for local and specific population is more urgently needed. This study aimed to determine the levels of trihalomethanes (THMs) and haloacetic acids (HAAs) in 16 public indoor swimming pools in Shanghai, China. Swimming habits were also investigated to obtain more accurate exposure assessment parameters. Precise exposure assessment through multiple pathways, resulting cancer risk, and disability-adjusted life years (DALYs) were assessed. Results indicated that the highest total level of THMs and HAAs occurred in autumn. The surveyed swimmers 9-17 years of age had higher average daily dose (ADD) of DBPs than swimmers ≥18 years of age. The total lifetime cancer risk (LCR) attributable to THMs and HAAs exceeded 10-6, which represents a negligible risk level (NRL). The cancer risk from inhalation exposure predominantly by THMs contributed more than 99% of the total risk. Annual disease burden was 19.0 person-years attributed to exposure of DBPs in swimming pool water in Shanghai. This study provides a paradigm and strategic reference of precise exposure assessments, risk assessments, and disease burden estimation of hazards in swimming pool water for other regions.

The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.

Disinfected drinking water contains hundreds of disinfection by-products (DBPs) that are formed by the reaction of disinfectants with natural and anthropogenic organic matter, bromide, and iodide. Understanding what these DBPs are is important because millions of people worldwide consume drinking water every day, and human epidemiologic studies have reported cancer, miscarriage, and birth defects from consuming such waters. While more than 600 DBPs are reported in the literature, very few studies quantify complete classes of chlorinated, brominated, and iodinated DBPs. Also, very few studies conduct comprehensive non-target analyses of unknown DBPs to characterize the complete DBP exposure (the exposome). We developed a new gas chromatography (GC)-mass spectrometry (MS) method that simultaneously quantifies 39 priority unregulated DBPs from six different chemical classes (haloacetaldehydes, haloketones, haloacetamides, haloacetonitriles, halonitromethanes, and iodinated-trihalomethanes) and analyzes unknown DBPs with mass accuracy600 ppm under full-scan conditions. Using a new type of time-of-flight (TOF) mass spectrometer, which combines selected ion monitoring (SIM)-level sensitivity with mass accuracy of ±0.05 Da, method detection limits of 3-61 ng/L were achieved. These levels were found to be quite comparable to those of a widely used single quadrupole mass spectrometer (2-90 ng/L) operated in SIM mode. However, analysis using this TOF mass spectrometer offers two additional advantages over traditional quadrupole-MS: (1) full-scan data, which provides additional confidence for target analytes, as well as complete mass spectra for unknown analysis, and (2) two decimal place mass accuracy, which allows additional confidence for target analytes and importantly, molecular formula indication for unknowns. High resolution accurate mass TOF was also used to validate identification of selected compounds. This new method was demonstrated on finished drinking waters from three different drinking water plants, where target quantification and non-target unknown analyses were performed simultaneously during the same run. This enabled the quantification of 39 DBPs, along with the non-target identification of many other drinking water contaminants, including two additional non-target DBPs: N,N-dimethylacetamide and N-nitrosodibutylamine.

Summary Background Systematic study of pemphigoid gestationis (PG) has not been performed owing to its rarity. Objectives To perform clinical and immunological analyses of 25 patients with PG. Methods In addition to clinical and histopathological assessments, we performed immunofluorescence (IF), immunoblotting (IB) and enzyme-linked immunosorbent assays (ELISAs). Results PG developed preferentially during the second or third trimester of pregnancy, with a mean age at onset of 30·5 years. Histopathology showed subepidermal blisters less frequently. Direct IF showed C3 deposition in the basement membrane zone (BMZ) in all patients, with rare reactivity with keratinocyte cell surfaces. Ninety-two per cent of patients showed circulating IgG anti-BMZ autoantibodies during indirect IF of either normal or 1 mol L−1 NaCl-split skin. Complement IF revealed linear C3 reactivity with the BMZ of normal skin in 68% of patients, and all patients had C3 reactivity on the epidermal side of 1 mol L−1 NaCl-split skin. IB and ELISA of the NC16a domain of BP180 recombinant protein was positive in 96% and 92% of patients, respectively, while only four patients had a positive ELISA for BP230. In IB tests, 28% of patients reacted with the C-terminal domain of BP180 and 20% reacted with leucocyte adhesion deficiency-1 protein. Multigravidae developed PG during a significantly (P

Summary CD69 has been known as an early activation marker of lymphocytes; whereas, recent studies demonstrate that CD69 also has critical functions in immune responses. Early studies using human samples revealed the involvement of CD69 in various inflammatory diseases including asthma. Moreover, murine disease models using Cd69−/− mice and/or anti-CD69 antibody (Ab) treatment have revealed crucial roles for CD69 in inflammatory responses. However, it had not been clear how the CD69 molecule contributes to the pathogenesis of inflammatory diseases. We recently elucidated a novel mechanism, in which the interaction between CD69 and its ligands, myosin light chain 9, 12a and 12b (Myl9/12) play a critical role in the recruitment of activated T cells into the inflammatory lung. In this review, we first summarize CD69 function based on its structure and then introduce the evidence for the involvement of CD69 in human diseases and murine disease models. Then, we will describe how we discovered CD69 ligands, Myl9 and Myl12, and how the CD69-Myl9 system regulates airway inflammation. Finally, we will discuss possible therapeutic usages of the blocking Ab to the CD69-Myl9 system.

ObjectiveParticipants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy.MethodsSubgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or ResultsSignificant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures.ConclusionsPubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy.ClinicalTrials.gov identifier:NCT00065806.

The presence of liver fibrosis is the common denominator in numerous chronic liver diseases that can progress to fibrosis and hepatocellular carcinoma. Most important, with respect to frequency, are viral hepatitis and non-alcoholic fatty liver disease, the prevalence of which is increasing in epidemic proportions. Liver biopsy, albeit imperfect, continues to be the criterion standard, but in many clinical situations tends to be replaced with noninvasive imaging methods.The aim of the present article was to describe our imaging department experience with magnetic resonance elastography and to analyze and discuss recently published results in gastroenterology, hepatology, and radiology from other authors in the literature, complemented with a PubMed search covering the last 10 years.Magnetic resonance elastography is an efficacious, noninvasive method with results that are concordant with liver biopsy. It is superior to ultrasound elastography because it evaluates a much greater volume of hepatic tissue and shows the often heterogeneous lesion distribution. The greatest advantage of the magnetic resonance protocol described is the fact that it quantifies fibrosis, fat content, and iron content in the same 25min examination specifically directed for that purpose, resulting in a favorable cost-benefit ratio for the patient and/or institution.

This study investigated the effects of mitiglinide in 16 patients with type 2 diabetes mellitus treated with 30 mg/day mitiglinide, divided into three doses given just before each meal, for approximately 12 months. A 450 kcal meal tolerance test was performed at baseline and after 3, 6 and 12 months, and levels of plasma glucose and immunoreactive insulin were measured. Various parameters of glucose metabolism and lipid metabolism, urinary albumin and markers of atherosclerosis, coagulation and fibrinolysis were also determined. Mitiglinide showed a rapid stimulatory effect on insulin secretion and reduced the levels of plasma glucose. The free fatty acid level significantly decreased at 60 min after the meal tolerance test. Mitiglinide also significantly lowered glycosylated haemoglobin and raised 1,5-anhydroglucitol after 6 months, and significantly decreased urinary albumin after 12 months. These data indicate that mitiglinide may have beneficial effects not only on glycaemic control but also on lipid metabolism and urinary albumin excretion, and may have a role in the prevention of the vascular complications of diabetes.

We evaluated the prevalence of exfoliation syndrome (ES) with or without glaucoma seen in our Department over a 32-month period. We could identify a total of 59 patients with ES, 30 males and 29 females. All the cases were aged 50 years or more except one case, with the peak in the 8th decade. The ages of the cases averaged 70.0 +/- 8.34 years. ES was present unilaterally in 47 cases (85%) and bilaterally in 12 (15%). Glaucoma was associated in 37 out of the 59 cases of ES (63%). Males with ES seemed to be more prone to develop glaucoma than females. We observed 96 non-ES cases with primary open angle glaucoma (POAG) during the same period. The ages of the cases averaged 59.6 +/- 15.4 years. Our survey indicates that ES is not an uncommon occurrence among the Japanese population served by our Department. The incidence of ES as a whole approximates three-fifths of that of POAG.

The object of this study was to generate cisplatin-conjugated gelatin microspheres (GMSs) and to confirm the subsequent release of cisplatin in vitro. The GMSs (1 mg) were immersed in 50 microl of a cisplatin solution (0.06, 0.15, 0.27, 0.30 or 0.54 mg ml(-1)) at 38 degrees C to allow conjugation. The cisplatin-conjugated GMSs were then extensively washed in double-distilled water and freeze-dried. The platinum concentration in the GMSs samples was investigated as a function of the concentration of cisplatin solution used in their preparation, the number of immersions in cisplatin (1, 2, 3, 4 or 5) and the period of immersion (1, 6 or 11 h). In vitro release tests were performed at different time intervals (1, 3, 6, 12 or 24 h) to allow the rate of cisplatin release to be calculated. The platinum concentration of the GMSs increased in proportion to the concentration of cisplatin solution and the length or number of immersions in cisplatin. In vitro release tests demonstrate that the release rate (%) from GMSs after 1, 3, 6, 12 or 24 h was 4.8, 5.5, 7.6, 10.0 and 12.4, respectively. We demonstrated the ability of GMSs to bind cisplatin forming cisplatin-conjugated GMSs. Moreover, we showed that cisplatin continued to bind GMSs strongly during the in vitro release test.

Aims Gastric cancer is a common and heterogeneous disease; however, global standard and biomarkers for selecting chemotherapy regimens have not been established. This study was designed retrospectively to identify molecular biomarkers for irinotecan plus S-1 (IRI-S) and S-1 therapy from subset analyses in GC0301/TOP-002, a randomised phase III trial for advanced gastric cancer. Materials and methods Paraffin-embedded primary tumour specimens were collected from 126 of 326 randomised patients in GC0301/TOP-002. The mRNA was measured for thymidylate synthase, dihydropyrimidine dehydrogenase, topoisomerase I, excision repair cross-complementing gene 1 (ERCC1) and thymidine phosphorylase; categorised into low and high to analyse their association with efficacy end points. Results There was no significant difference in each mRNA between S-1 and IRI-S groups, whereas there were differences among some clinical characteristics. Multivariate analyses for overall survival showed that mRNA levels were not correlated with prognosis. By comparison, between IRI-S and S-1 arms, low thymidylate synthase, low ERCC1 and high thymidine phosphorylase were associated with better prognosis for IRI-S versus S-1 (hazard ratio = 0.653, 0.702 and 0.709, respectively; P Conclusion Low thymidylate synthase, low ERCC1 and high thymidine phosphorylase are candidates for predictive biomarkers for first-line treatment in advanced gastric cancer by IRI-S. Further study is warranted to confirm these results in other clinical trials and cohort studies.

To investigate the relationship of dental status to food diversity among older Japanese.A community-based cross-sectional study conducted in the town of Tosa, Kochi Prefecture, Japan.The study participants were 252 Japanese (84 men and 168 women, average age 81.2 years) and dentate participants were classified into three groups: 1-9 teeth, 10-19 teeth and 20 or more teeth. Food diversity was assessed as a validated measure of dietary quality using the 11-item Food Diversity Score Kyoto (FDSK-11), which evaluates frequency of consumption of 11 main food groups. Multivariable analysis of the differences in FDSK-11 score ranging from 0 to 11, with a higher score indicating greater food diversity, among the three dental status groups was conducted using general linear models. All the performed analyses were stratified by gender.There was no association between dental status and food diversity score in models for men. In contrast, women with ≤ 9 teeth and with 10-19 teeth had significantly lower FDSK-11 scores than women with ≥ 20 teeth after adjusting for confounders (p0.001 and p = 0.009, respectively). Additionally, there was a trend toward lower scores for FDSK-11 with fewer teeth (p = 0.001).A less varied diet, as indicated by low FDSK-11 score, was observed in female participants with fewer teeth. Tooth loss was associated with poor diet quality among older Japanese women.

Natural killer type-1 (NK1)/NK2 terminology was proposed as an analogy to T helper type-1 (Th1)/Th2 subsets of CD4 T cells. In addition to well recognized IFN-gamma-producing NK1 cells, recent accumulating evidence suggests the presence and the regulatory function of NK2 cells, which produce type-2 cytokines, such as IL-5 and IL-13. Most studies on the production of cytokines by NK1/NK2 subsets have been performed in the human system. Recently, a mouse in vitro NK1/NK2 cell differentiation system was established. A linear 2-0-1 model has been proposed for the differentiation of NK1/NK2 cell subsets, but the branching NK1/NK2 cell differentiation model, comparable to Thl/Th2 cell differentiation, remains a likely explanation. In this review, we summarize the evidence indicating the unique features of NK1/NK2 cells and discuss the above two NK cell differentiation models. In addition, we point to interesting similarities in the expression of transcription factors that regulate cytokine production in NK cells and CD8 T cells.

Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor beta, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2-deficient mice, mature peripheral T cells exhibited normal anti-T cell receptor-induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2-deficient developing Th2 cells showed constitutive activation of nuclear factor kappaB (NF-kappaB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-kappaB for binding to a consensus NF-kappaB motif and inhibit NF-kappaB-driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-kappaB function.

We report herein a rare case of malignant gastrointestinal stromal tumor (GIST) originated from the rectal wall, which presented as a tumor on the rectovaginal septum.A 54-year-old Japanese woman, gravida 4, para 3, was admitted complaining of anuresis and severe constipation. She had a history of hysterectomy and right salpingo-oophorectomy for uterine leiomyoma 11 years previously. Pelvic examination revealed an 8.5 × 7.5 × 7.5 cm hard mass in the rectovaginal space. The inferior border of the tumor was 2 cm from the vaginal introitus and 2 cm from the anus. Computed tomography and magnetic resonance imaging showed a well-circumscribed soft-tissue mass filling the rectovaginal space. Urinary bladder and rectum were markedly compressed and displaced. Colon fiberscopy revealed invasion of the tumor into the rectal mucosa. An abdominoperineal resection of the rectum with posterior vaginal wall resection and pelvic lymphadenectomy was performed. The resected specimen showed a rectal submucosal tumor that was 8 × 8 × 7 cm in size. The tumor was diagnosed as a malignant GIST. Immunohistochemical analysis confirmed this diagnosis. The patient is now healthy without evidence of recurrence at 13 months after surgery.Gynecologists should be aware of rectal GIST arising in the rectovaginal space as a differential diagnosis of vaginal submucosal tumor.

Background: Certain immune functions are known to be impaired in human beings exposed to Antarctic winter; in particular, decreased amounts of serum proinflammatory cytokines, such as TNF-α and IL-1, were noted. It is not known, however, whether this exposure has any effect on T-cell-mediated acquired immune functions. Objectives: This study aims to investigate whether exposure to Antarctic winter has any effect on T cell-dependent immune functions. Methods: We assessed changes in various immunologic indicators, including serum levels of various cytokines, peripheral blood Vα24Vβ11 natural killer T cell numbers, and T H 1/T H 2 ratios of 40 Japanese personnel exposed to an Antarctic winter. Also, a 2-month inland traverse was executed during the isolation, and the effect on the above indicators was assessed. Results: All subjects were healthy during the Antarctic isolation. The levels of serum TNF-α, IL-1Ra, IL-6, and IL-1β were dramatically reduced and remained at low levels throughout the isolation. The decrease in the levels of TNF-α and IL-1Ra was more pronounced during the inland traverse than during the rest of the isolation. The percentage of Vα24Vβ11 natural killer T cells was significantly increased at the midpoint of the isolation. Most interestingly, T H 1/T H 2 ratio was increased significantly, and this T H 1 bias was most prominent at the late point of the isolation. Conclusions: Exposure to an Antarctic winter appeared to induce T H 1-skewed immunity in human beings. (J Allergy Clin Immunol 2003;111:1353-60.)

Using cross-sectional and prospective analyses, the risk factors for macroangiopathy (MA) in nonobese Type 2 diabetic patients were evaluated. In the cross-sectional study, we determined a cutoff point for each variable at which changes in the prevalence of total MA reached statistically significant levels. In the prospective study, those who met more than four out of seven control criteria as set forth in the Multiclinical Study for Diabetic Macroangiopathy (MSDM) had less risk of MA in Type 2 diabetes initially diagnosed without MA compared with those who fulfilled less than three factors. These results suggest that multiple risk factor control is the most effective and reasonable way to lower the incidence of MA in Type 2 diabetes.

Background Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to orthopedic surgeons. Nonunion and lengthy wound healing in high-risk patients with diabetes, particularly patients with peripheral arterial disease and renal failure, occur secondary to several clinical conditions and are often fraught with complications. Whether diabetic ankle fractures are best treated noninvasively or surgically is controversial. Case presentation A 53-year-old Japanese man fractured his right ankle. The fractured ankle was treated nonsurgically with a plaster cast. Although he remained non-weight-bearing for 3 months, radiography at 3 months showed nonunion. The nonunion was treated by Ilizarov external fixation of the ankle. The external fixator was removed 99 days postoperatively, at which time the patient exhibited anatomical and functional recovery and was able to walk without severe complications. Conclusion In patients with diabetes mellitus, severe nonunion of ankle fractures with Charcot arthropathy in which the fracture fragment diameter is very small and the use of internal fixation is difficult is a clinical challenge. Ilizarov external fixation allows suitable fixation to be achieved using multiple Ilizarov wires.

Purpose: To clarify the Doppler sonographic features of the lingual artery in normal subjects and to evaluate those of patients with cancer of the tongue. Material and Methods: Sixty-seven volunteers and 12 patients with cancer and/or leukoplakia of the tongue were examined with an intraoral sonographic probe. The visibility of the deep lingual artery was determined on transverse and anteroposterior images. On the transverse images, the vascular index, which was defined as the number of colored pixels, was measured on bilateral lingual arteries. Thereafter, the degree of symmetry was evaluated for normal subjects and patients. Results: In normal subjects, between younger and older volunteers, there were no significant differences in visibility of the trunk but differences were found between the two groups for the dorsal branches. The vascular indices of the right and left sides were not different. The characteristic Doppler sonographic feature was vasculature in and around the tumors in the patients with cancer of the tongue. The symmetry indices of the cancer patients were significantly different from those of normal subjects. Conclusion: Doppler sonography should be an important procedure for evaluation of tongue neoplasms.

Objectives: The body’s response to stress is comprised of two opposing reactions, namely inflammation and immunosuppression. The balance between these two reactions not only changes over time, but also varies among different cells or organs. Limited information is available regarding the cytokine balance of circulating blood and inflammatory sites after thoracic surgical stress. Design: The subjects of the present study were 10 patients undergoing esophageal cancer surgery which requires thoracolaparotomic manipulation. The postoperative levels of interleukin (IL)-8, IL-10, IL-1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor I (sTNF-RI) in bronchoalveolar lavage fluids (BALFs) and peripheral blood were measured by enzyme-linked immunosorbent assay. The absolute concentration of cytokines in lower respiratory tract ([cytokine]LRT) was estimated by using the ratio of urea concentration in BALF and serum. Results: The levels of these cytokines in peripheral blood peaked within 24 h of start of the surgery (IL-8 85.6 ± 29.8 pg/ml; IL-10 65.1 ± 10.6 pg/ml; IL-1ra 2,807.8 ± 652.8 pg/ml, and sTNF-RI 3,996.3 ± 380.1 pg/ml). The level of [IL-8]LRT immediately after surgery was approximately 20 times higher than that in peripheral blood, and the level of [IL-1ra]LRT was approximately 4 times higher. In contrast, the level of [IL-10]LRT immediately after surgery was comparable to that in peripheral blood, but the level of [sTNF RI]LRT immediately after surgery was approximately one fifth of that in peripheral blood. Conclusions: The balance between pro- and anti-inflammatory reactions varies from one part of the body to the next, and changes over time after surgery. The profile of stress-induced pro-inflammatory cytokines and anti-inflammatory cytokines should be analyzed further to establish appropriate and effective cytokine modulatory therapeutic approaches.

A new exercise protocol has been proposed, with respect to cardiopulmonary exercise testing, which starts at a low work rate (WR) and increases exponentially by a standard percentage of the previous work rate every minute: the test is termed STEEP (standardised exponential exercise protocol). The potential advantage of this protocol is that it can accommodate a wide range of subjects, since it allows a maximum to be attained with a relatively narrow variation of tolerance time, regardless of subjects exercise capacity. To date, only the VO 2max has been compared with that from the current standard ramp protocol. The ramp, however, also allows other important parameters of aerobic function to be estimated: the anaerobic threshold (AT); the response time constant; and ΔVO2/ΔWR. The aim of this study was, therefore, to clarify whether these aerobic parameters can be readily discerned from the responses to the STEEP protocol both from a theoretical and practical viewpoint. As a result of theoretical considerations, we demonstrated that the VO2 time constant and ΔVO2/ΔWR may not both be estimated uniquely. As a practical expedient, a procedure was proposed for estimating the parameter analogues. The preliminary results for six subjects between the STEEP and ramp protocols showed consistent positive correlation for VO 2max (r=0.997) and AT-VO2 (r=0.980), whereas the correlation for the VO2 time constant and ΔVO2/ΔWR were not significant. Further study is needed to clarify the reason(s) for the discrepancies both from a theoretical and practical viewpoint.

Cilostazol(6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4- dihydro-2(1H)-quinolinone) selectively inhibits cGMP-inhibited phosphodiesterase (PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation (SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE1 and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg cilostazol to healthy volunteers produced a significant inhibition of SIPA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment of arterial occlusive diseases.

We investigated the usefulness of Amplicor HCV assay and branched DNA probe assay in efficacy evaluation of interferon therapies for chronic hepatitis C. Subjects were 164 HCV-RNA positive chronic hepatitis C patients who received interferon-alpha (IFN-alpha, HLBI) 3-6 MU per day for 14-24 weeks. Their HCV-RNA levels were examined five times by using reverse transcription-polymerase chain reaction (RT-PCR) assay, Amplicor HCV assay, and branched DNA probe assay. Complete response rate in the low virus level patients was significantly higher than in the high virus level patients (P0.001). In complete responders, the rate of HCV-RNA disappearance 2 weeks after the initiation of IFN therapy was higher than in non-responders (P0.001). The HCV-RNA positive rates in RT-PCR assay and Amplicor HCV assay agreed by 98% or more. The HCV-RNA negative patients 6 months later were still negative 12 months later by Amplicor HCV assay. Before starting interferon therapy for chronic hepatitis C, it is advisable to make a prediction of treatment efficacy by using branched DNA probe assay. In addition, disappearance of HCV-RNA after 2 weeks of treatment could be a useful predictor of the therapeutic efficacy of IFN. Amplicor HCV assay is useful in detecting HCV-RNA and for efficacy evaluation during and after a given interferon therapy.

Background Little is known about the timing of polyomavirus reactivation and its presence in urine after renal transplantation. The purpose of this study was to investigate the prevalence of positive polyomavirus in urine at various time points after renal transplantation. Methods From November 2008 to August 2013, 279 renal transplant patients from our institution were included in this study. One urine sample was collected at 0–3, 4–6, 7–12, 13–24, 25–60, and ≥61 months after renal transplantation. A total of 394 urine samples were assessed for the presence of the BK and JC viruses with the use of a real-time polymerase chain reaction assay. Results BK virus was detected in the urine of one-third of patients during the first 6 months. Thereafter, the positivity rate decreased gradually to 12% >5 years after transplantation. The positivity rate for the JC virus in urine was 33%–49% regardless of the post-transplantation phase. Conclusions BK virus was detected more frequently in urine during the early phase after renal transplantation, whereas the JC virus was detected more consistently.

To diagnose hepatocellular carcinoma (HCC) functionally and immediately, we examined the usefulness of indocyanine green (ICG) injection during ultrasound-guided liver biopsy. Liver specimens were obtained after intravenous ICG injection by ultrasound-guided biopsy from 251 space-occupying lesions (SOL) in 136 patients. The tissues were immediately examined for ICG uptake using an infrared Vidicon camera and were also subjected to histopathological examinations. Of the 112 ICG-negative biopsy specimens, 105 were histologically diagnosed as HCC, 6 as dysplastic nodules (DN) and 1 as a regenerative nodule (RN). Of the 139 ICG-positive specimens, 18 were diagnosed as HCC, 1 as DN and 120 as RN. The sensitivity of the absence of ICG uptake (SEAIU), the specificity of the absence of ICG uptake (SPAIU), and the positive predictive value of the absence of ICG uptake (PPAIU) for the diagnosis of HCC were 85.3%, 94.5% and 93.8%, respectively. Of the 251 SOLs, 184 were less than 2 cm. SEAIU, SPAIU and PPAIU for the diagnosis of these small HCC were 85.3%, 94.5% and 91.4%, respectively. These results support the reliability of ICG injection during ultrasound-guided liver biopsy to diagnose even small HCC.

We report surgical techniques for single-incision laparoscopy-assisted surgery (SILAS) in the treatment of pediatric acute appendicitis.We performed SILAS in 15 cases of acute appendicitis between January and September of 2009. SILAS is a surgical method that involves making the incision at the umbilicus, inserting a wound retractor XS, suspending the abdominal wall with a hook, and appendectomy with the same procedures as conventional appendectomy.SILAS appendectomy was performed in all 15 cases with the exception of one case where one 3-mm port was added. Compared to open appendectomy, blood loss was significantly lower and postoperative hospitalization time was shorter, although there was no significant decrease in operative time, or postoperative fasting time. No postoperative complications, such as wound infection, intestinal obstruction, intra-abdominal abscess, or bleeding, were encountered.SILAS was safely performed and is superior to open appendectomy with regard to cosmetic outcome.

Objective Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. Methods A total of 221 participants with pediatric SLE (ages 10–21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n = 113) or placebo (n = 108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. Results Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P = 0.24). The atorvastatin group achieved lower hsCRP (P = 0.04), total cholesterol (P < 0.001), and low-density lipoprotein (P < 0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023–0.0144 mm/year; P < 0.05). Serious adverse events and critical safety measures did not differ between groups. Conclusion Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

Two distinct cDNAs encoding bradykinin receptors (BKRs) were cloned from NG108-15 neuroblastoma-glioma hybrid cells. One was identical with rat uterus B2 BKR, whereas the other one (mBKR) had 91% amino acid homology to the rat B2 BKR and 82% homology to human B2 BKR. Southern blot analysis and genomic DNA cloning revealed that mBKR is derived from the mouse genome. The mBKR, expressed in Xenopus oocytes and COS-7 cells, produced functional BKRs that exhibited the properties of smooth muscle type B2 BKR. These results suggest that both the rat and mouse B2 BKRs of the smooth muscle type are expressed in NG108-15 cells.

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.

Oral and maxillofacial surgery, which involves several sharp instruments and fixation materials, is consistently at a high risk for cross-contamination due to perforated gloves, but it is unclear how often such perforations occur. This study aimed to address this issue. The frequency of the perforation of surgical gloves (n=1436) in 150 oral and maxillofacial surgeries including orthognathic surgery (n=45) was assessed by the hydroinsufflation technique. Orthognathic surgery had the highest perforation rate in at least 1 glove in 1 operation (91.1%), followed by cleft lip and palate surgery (55.0%), excision of oral soft tumour (54.5%) and dental implantation (50.0%). The perforation rate in scrub nurses was 63.4%, followed by 44.4% in surgeons and first assistants, and 16.3% in second assistants. The odds ratio for the perforation rate in orthognathic surgery versus other surgeries was 16.0 (95% confidence interval: 5.3-48.0). The protection rate offered by double gloving in orthognathic surgery was 95.2%. These results suggest that, regardless of the surgical duration and blood loss in all fields of surgery, orthognathic surgery must be categorized in the highest risk group for glove perforation, following gynaecological and open lung surgery, due to the involvement of sharp objects.

Prognosis of patients with recurrent esophageal cancer is usually unsatisfactory. We have successfully treated five patients with cervical node recurrence after esophagectomy with multimodal treatment including salvage lymphadenectomy. In order to clarify the efficacy of salvage surgery for cervical node recurrence, we have reviewed the clinical course and prognosis of these patients. From August 2004 to December 2007, 30 patients with 33 recurrent sites were treated in the Department of Surgery, Iizuka Hospital. Among these patients, there were five patients with recurrence limited within the cervical nodes. Salvage cervical lymphadenectomy was performed for all five patients. Curative resection was achieved in four patients and reduction surgery followed by planned chemoradiotherapy was performed in another patient. All stations including the suspicious node were dissected and a partial sternotomy was added for one patient whose recurrent tumor was located in the right recurrent nerve node. There was no mortality and one minor complication (subcutaneous hemorrhage) was observed. Median duration of hospital stay was 7 days. Adjuvant chemotherapy was performed for all patients. Median follow-up period was 54 months and all patients are alive without relapse of the disease. Salvage cervical lymphadenectomy is a safe and effective treatment for patients with cervical node recurrence after esophagectomy.

Hepatocellular carcinoma (HCC) shares only a small proportion of hyperechoic liver tumors detected in MHTS and mimics hemangioma on ultrasonography (US). The precise diagnosis of HCC is hence difficult in MHTS, but presence or absence of underlying chronic liver disease and serum alfa-fetoprotein (AFP) titer might provide useful informations.

A 25-year-old Japanese man presented with high spiking fever, arthralgia and a skin rash. A pruritic edematous erythema with persistent plaques was found mainly on the trunk; these lesions persisted even when the fever subsided, with prominent linear pigmentation. As marked neutrophilia and a high level of serum ferritin were detected, a diagnosis of adult-onset Still’s disease (AOSD) was made, even though the persistent eruption was not characteristic of the disease. Oral prednisolone, together with low-dose methotrexate, was given with good results. In the literature, a similar atypical rash has been reported in 11 cases in Japan. All of them required high-dose administration of corticosteroids or other immunosuppressive agents. Severe systemic complications were seen in 3 patients, and 2 cases died of the disease. Persistent plaques and linear pigmentation are some of the manifestations of AOSD, which cannot be overlooked. This appearance could be an indication that suggests an increased risk of systemic complications and a prolonged time to clinical remission.

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R2 for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Autoimmune pancreatitis represents a chronic inflammatory pancreatic disease with distinct clinical, morphologic and histopathological features. We report the case of a 64 year old man with obstructive jaundice in whom the imaging studies showed diffuse enlargement of the pancreas, and a mass in its head. Fine needle aspiration biopsy of the mass guided by endoscopic ultrasound showed lymphocytic infiltration and fibrosis. The size of the pancreas, laboratory abnormalities, and clinical manifestations subsided promptly after treatment with steroids. Autoimmune pancreatitis should be included in the differential diagnosis of patients with obstructive jaundice and/or pancreatic masses.

The aim of the present study was to evaluate the long-term outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD) and its effect on chest pain. Between June 1995 and August 2009, a total of 35 patients with achalasia underwent an LHD. The symptom scores were calculated by combining the frequency and the severity. Pre- and postoperative evaluations included symptom score, radiology, manometry, and 24-hour pH manometry. Median total symptom score was significantly lower than the preoperative score (19 vs 4, P0.001) at a median follow-up of 94 months. Among the 35 patients, 18 (51%) had chest pain. The frequency of chest pain was similar for the pre- and postoperative scores, but the severity tended to be less. Median esophageal diameter (5.4 cm vs 3.5 cm, P0.001) and lower esophageal sphincter pressure (41 mmHg vs 8.9 mmHg, P0.001) were significantly reduced after surgery. Median age, duration of symptoms, esophageal diameter, and lower esophageal sphincter pressure were similar between patients with and without chest pain prior to surgery. No significant differences were observed between the two groups in terms of amplitude, duration, and frequency of contractions from the findings of postoperative 24-hour esophageal manometry. Chest pain resolved in three patients (17%) and improved in seven patients (39%) after surgery. LHD can durably relieve achalasic symptoms of both dysphagia and regurgitation, and it can be considered the surgical procedure of choice. However, achalasic chest pain does not always seem to be related with patient characteristics and manometric findings.

The aim of this study was to evaluate the indications for pulmonary resection (lobectomy) in patients with increased total pulmonary vascular resistance (TPVR) during a preoperative unilateral pulmonary artery occlusion (UPAO) test. According to our previous report, the feasibility of performing lobectomy in patients with a high risk of cardiopulmonary complications is determined on the basis of the increase in TPVR after 15 min of obstruction during the UPAO test (occluded TPVR).A total of 19 high-risk [occluded TPVRor =700 dynes/s/cm(-5)/m(2) (dynes)] patients who underwent lobectomy or pneumonectomy were studied and a detailed analysis of postoperative cardiopulmonary complications was performed. The subjects were divided into four groups based on the occluded TPVR (700-799 dynes, 800-899 dynes, 900-999 dynes, oror =1000 dynes) to compare the incidence of postoperative complications.Two patients died after surgery. One of them had an occluded TPVR1000 dynes and died 313 days after right upper lobectomy; the other had an occluded TPVR of 783 dynes and died 20 days after right pneumonectomy. Postoperative cardiopulmonary complications occurred in 6 of 19 patients (31.6%), and all three patients with an occluded TPVRor =900 dynes developed cardiopulmonary complications.Limited surgery should be performed in patients with an occluded TPVRor =900 dynes.