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This study aimed to evaluate the cost-effectiveness of bariatric surgery (BS) compared to non-surgical treatment (NST) in Korean people with morbid obesity according to comorbidities and body mass index (BMI) severity. The target cohort was people with morbid obesity, defined as BMI of ≥ 35 kg/m2, or obese people with BMI of 30–34.9 kg/m2 having obesity-related comorbidities. A decision-tree model for 1-year obesity treatment and Markov model for the rest of life were used. In the decision-tree model, the comorbidity remission rate and BMI change after 1-year treatment were decided based on a prospective clinical trial. In the Markov model, the transition probabilities were calculated considering the BMI level and age. The starting age of 20 years, a cycle length of 1 year, a time horizon of 80 years, and a 5% discount rate were applied for the base case from the healthcare system perspective. In the base case, BS improved quality-adjusted life years (QALYs) and was the cost-effective option in total cohort (incremental cost-effectiveness ratio of BS vs. NST was 674 USD/QALY). It was shown to be cost-effective in all subgroup analyses based on BMI level. In particular, BS was a dominant alternative for the subgroup with basal BMI of 35.0–37.4 kg/m2. Various sensitivity analyses showed the robustness of results indicating the cost-effectiveness of BS. BS at BMI of > 30 kg/m2 was more effective than NST for a reduction in BMI and remission of obesity-related comorbidities and was cost-effective in Korea.

Korea has the highest burden of tuberculosis (TB) among Organization for Economic Co-operation and Development countries. Various strategies have been implemented to eradicate TB in Korea, and it is critical to evaluate previous TB management outcomes before framing future TB policies. Over the past few decades, the rapid increase in the aging population in Korea has substantially impacted the incidence of TB among the elderly. Thus, in this study, we aimed to develop a mathematical model for the assessment of TB management outcomes incorporating special features of TB transmission dynamics in Korea. First, we incorporate 2-age groups in our TB model because TB epidemics in Korea are different between the elderly and the non-elderly (&lt, 65 years vs. ≥65 years). Second, because the public-private mix has had a full-fledged impact since 2012, this study was divided into two periods (2001–2011 and 2012–2018). We developed a mathematical model of TB transmission dynamics with 2-age groups and age-specific model parameters were estimated based on actual TB epidemic data from 2001 to 2018. These parameters included transmission rates, relapse rates, and recovery rates. We conducted sensitivity analyses of various parameters, and investigated the impacts of these parameters on TB incidence. Our results demonstrate that the overall outcomes of both age-groups improved in the period of 2012–2018 compared with that in the period of 2001–2011. Age-specific interventions should be implemented to reduce the overall TB incidence. More intensive treatment efforts should be focused on the elderly, while the early detection and treatment rates for latent TB were the most significant factor to reduce TB incidence in both groups.

Aim Subsequent cancers (SCs) after melanoma diagnosis further increases the risks of mortality and medical costs. This population-based analysis aimed to evaluate risk factors for SC, mortality, and medical costs of melanoma patients with SC. Methods A retrospective cohort analysis was conducted using a nationwide claims database during 2002-2017 in South Korea. SC was defined as having other types of cancer diagnoses other than subsequent melanoma during-up to 5 years after melanoma diagnosis. Melanoma patients were divided into patients with and without SC, and the overall and subgroup survival rates, the risk of developing SC, and the total medical costs were analyzed using a Kaplan-Meier method and regressions. Results A total of 3740 melanoma patients were included in the analysis (mean age, 62.3 ± 15.4 y; 47.2% men), and 2273 patients (1157 within 2 months, 756 after 2 months of melanoma diagnosis) had SC. Higher Charlson comorbidity index score and male sex significantly increased the risk of developing SC. Five-year survival rate and cumulative medical costs were 62.3% (95% confidence interval [CI], 60.8-63.9) and $21,413, respectively, in all patients. Patients with SC diagnosed after 2 months showed the lowest survival rate of 47.8% (95% CI, 44.3-51.4) and the highest costs of $27,081, showing a mortality hazard ratio of 1.65 (range, 1.46-1.86) and a cost ratio of 1.189 (range, 1.112-1.271) compared with those without SC. Conclusion This study presented survival outcomes and medical costs in melanoma patients and confirmed that SC after the first diagnosis of melanoma significantly increased disease burden in terms of mortality and medical costs.

Background: Tuberculosis (TB) has significant effects on patients’ health-related quality of life (HRQOL) and this study was conducted to evaluate the HRQOL based on EQ-5D utility score according to various health statuses of TB patients.Methods: A systematic literature review was conducted to select articles on HRQOLs outcomes of TB patients since 2000. A total of 1,710 articles were searched for primary screening and seven studies that directly assessed all types of TB patients using the EQ-5D were finally selected.Results: The EQ-5D scores of TB patients were in the ranges of 0.43–0.70. After the completion of TB treatment, the utility weights increased to the ranges of 0.88–0.98 and the EQ VAS values showed similar trend as the results of the EQ-5D. The EQ-5D score for multi-drug-resistant TB was very low at 0.51 during treatment but increased to 0.88 after the treatment was completed. The utility weights of latent TB were not significantly different from those of the general population.Conclusion: This study showed that the HRQOL based on the EQ-5D utility score of TB patients has significantly decreased, and the TB treatment has a significantly positive effect on the quality of life of patients.

The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, reflecting the unique properties of Clec9A as a receptor specialized for delivery of antigens for cross-presentation. We reveal RNF41 is a negative regulator of Clec9A and the cross-presentation of dead cell-derived antigens by mouse dendritic cells. Intriguingly, RNF41 regulates the downstream fate of Clec9A by directly binding and ubiquitinating the extracellular domains of Clec9A. At steady-state, RNF41 ubiquitination of Clec9A facilitates interactions with ER-associated proteins and degradation machinery to control Clec9A levels. However, Clec9A interactions are altered following dead cell uptake to favor antigen presentation. These findings provide important insights into antigen cross-presentation and have implications for development of approaches to modulate immune responses.

Background It is essential to have information on the disease burden of lung cancer at an individual level throughout the life; however, few such results have been reported. Thus, this study aimed to assess the lifetime disease burden in patients with lung cancer by assessing various factors, such as survival, years of life lost (YLL) and medical expenditure in South Korea based on real-world data and extrapolation. Methods Newly diagnosed lung cancer patients (n = 2919) in 2004–2010 were selected and observed until the end of 2015 using nationwide reimbursement claim database. The patients were categorised into the Surgery group, Chemo and/or Radiotherapy group (CTx/RTx), and Surgery+CTx/RTx according to their treatment modality. Age- and sex-matched control subjects were selected from among general population using the life table. The survival and cost data after diagnosis were analysed by a semi-parametric method, the Kaplan–Meier analysis for the first 100 months and rolling extrapolation algorithm for 101–300 months. YLL were derived from the difference in survival between patients and controls. Results Lifetime estimates (standard error) were 4.5 (0.2) years for patients and 14.5 (0.1) years for controls and the derived YLL duration was 10.0 (0.2) years. Lifetime survival years showed the following trend: Surgery (14.2 years) > Surgery+CTx/RTx (8.5 years) > CTx/RTx group (3.0 years), and YLL were increased as lifetime survival years decreased (2.3, 8.7, 12.2 years, respectively). The mean lifetime medical cost was estimated at 30,857 USD/patient. Patients in the Surgery group paid higher treatment cost in first year after diagnosis, but the overall mean cost per year was lower at 4359 USD compared with 7075USD of Surgery+CTx/RTx or 7626USD of CTx/RTx group. Conclusions Lung cancer has resulted in about 10 years of life lost in overall patients. The losses were associated with treatment modality, and the results indicated that diagnosing lung cancer in patients with low stage disease eligible for surgery is beneficial for reducing disease burden in terms of survival and treatment cost per year throughout the life.

After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.

OBJECTIVES: To provide an overview and quantitatively demonstrate the reach of the Health Resources and Services Administration’s Maternal and Child Health Bureau autism research program. METHODS: We reviewed program reports and internal data from 59 autism research grantees. The US federal Interagency Autism Coordinating Committee’s strategic plan questions were used as a framework to highlight the contributions of the autism research program in advancing the field. RESULTS: The autism research program grantees advance research in several ways. Grantees have strengthened the evidence for autism interventions by conducting 89 studies at 79 distinct research sites. A total of 212 708 participants have enrolled in autism research program studies and 361 researchers have contributed to furthering autism research. The program addresses topics that align with the majority of the Interagency Autism Coordinating Committee’s priority topic areas, including advancements in treatments and interventions, services and supports, and identifying risk factors. Grantee products include 387 peer-reviewed publications, 19 tools, and 13 practice guidelines for improving care and intervention practices. CONCLUSIONS: The autism research program has contributed to medical advances in research, leveraged innovative training platforms to provide specialized training, and provided access to health services through research-based screening and diagnostic procedures. Autism research program studies have contributed to the development of evidence-based practice guidelines, informed policy guidelines, and quality improvement efforts to bolster advancements in the field. Although disparities still exist, the Health Resources and Services Administration’s Maternal and Child Health Bureau can reduce gaps in screening and diagnosis by targeting interventions to underserved populations including minority and rural communities.

Targeting model antigens (Ags) to Clec9A on DC has been shown to induce, not only cytotoxic T cells, but also high levels of Ab. In fact, Ab responses against immunogenic Ag were effectively generated even in the absence of DC-activating adjuvants. Here we tested if targeting weakly immunogenic putative subunit vaccine Ags to Clec9A could enhance Ab responses to a level likely to be protective. The proposed “universal” influenza Ag, M2e and the enterovirus 71 Ag, SP70 were linked to anti-Clec9A Abs and injected into mice. Targeting these Ags to Clec9A greatly increased Ab titres. For optimal responses, a DC-activating adjuvant was required. For optimal responses, a boost injection was also needed, but the high Ab titres against the targeting construct blocked Clec9A-targeted boosting. Heterologous prime-boost strategies avoiding cross-reactivity between the priming and boosting targeting constructs overcame this limitation. In addition, targeting small amounts of Ag to Clec9A served as an efficient priming for a conventional boost with higher levels of untargeted Ag. Using this Clec9A-targeted priming, conventional boosting strategy, M2e immunisation protected mice from infection with lethal doses of influenza H1N1 virus., Vaccine technology: targeting the vaccine to the immune system Duration and intensity of vaccine response can be boosted using antibodies to target pathogen fragments to specific immune system cells. Dendritic cells exist to take fragments of infectious diseases and present them to the immune system, sparking host defenses. Now, researchers led by Monash University’s Mireille Lahoud, and Ken Shortman of the Walter and Eliza Hall Institute, have successfully used antibodies to target fragments of influenza and hand, foot and mouth disease directly to dendritic cell molecules, specifically chosen to elicit a prolonged immune response. Mice inoculated with the targeted vaccine were protected from lethal influenza exposure, whereas the hand, foot and mouth disease vaccine elicited promising, but less marked results. With further development, this technology could provide a vital boost to vaccines that offer poor immunity on their own.

Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. From a South Korean national health insurance sample cohort database for 2002–2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28–1.55) and 2.17 (1.84–2.57) for parkinsonism and 2.87 (2.30–3.58) and 4.75 (3.39–6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson disease. Medications potentially associated with parkinsonism were assumed to increase the risk for parkinsonism/Parkinson disease, but more studies are required to confirm this relationship.

// Jung Ku Jo 1, * , Jong Jin Oh 2, * , Yong Tae Kim 1 , Hong Sang Moon 3 , Hong Yong Choi 3 , Seunghyun Park 4 , Jin-Nyoung Ho 5 , Sungroh Yoon 4 , Hae Young Park 1 and Seok-Soo Byun 2 1 Department of Urology, Hanyang University Hospital, Seoul, Korea 2 Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 3 Department of Urology, Hanyang University Guri Hospital, Guri-si, Korea 4 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea 5 Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea * These authors contributed equally to this work Correspondence to: Seok-Soo Byun, email: ssbyun@snubh.org Hae Young Park, email: nopcme@hanyang.ac.kr Keywords: metastasis, prostate cancer, castration, genetic variation Received: December 14, 2016 Accepted: May 01, 2017 Published: May 30, 2017 ABSTRACT Background: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions: Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.

An optimized therapeutic regimen involving a non-ablative fractionated laser or radiofrequency therapy for acne scars has not yet been established. To evaluate whether the combination of a non-ablative fractional laser (NAF) and fractional micro-needling radiofrequency (FMR) has clinical advantages for the treatment of atrophic acne scars compared with NAF alone, a 16-week prospective, randomized split-face study was performed. Each facial side of a patient was treated with 3 sessions of either NAF with FMR or NAF alone, with a 4-week interval between each session. Although both sides demonstrated significant decreases in the échelle d’évaluation clinique des cicatrices d’acné (ECCA) score, the facial side treated using the combination regimen demonstrated greater improvement in ECCA score regarding degree and onset time than the NAF-treated side. Histopathological and immunohistochemical results confirmed the clinical findings. This study demonstrated that a combination regimen involving NAF and FMR could be a viable option with satisfactory efficacy.

BACKGROUND To assess the cost-effectiveness of drug therapy to prevent osteoporotic fractures in postmenopausal women with osteopenia in Korea. METHODS A Markov cohort simulation was conducted for lifetime with a hypothetical cohort of postmenopausal women with osteopenia and without prior fractures. They were assumed to receive calcium/vitamin D supplements only or drug therapy (i.e., raloxifene or risedronate) along with calcium/vitamin D for 5 years. The Markov model includes fracture-specific and non-fracture specific health states (i.e. breast cancer and venous thromboembolism), and all-cause death. Published literature was used to determine the model parameters. Local data were used to estimate the baseline incidence rates of fracture in those with osteopenia and the costs associated with each health state. RESULTS From a societal perspective, the estimated incremental cost-effectiveness ratios (ICERs) for the base cases that had T-scores between -2.0 and -2.4 and began drug therapy at the age of 55, 60, or 65 years were $16,472, $6,741, and -$13,982 per quality-adjusted life year (QALY) gained, respectively. Sensitivity analyses for medication compliance, risk of death following vertebral fracture, and relaxing definition of osteopenia resulted in ICERs reached to $24,227 per QALY gained. CONCLUSIONS ICERs for the base case and sensitivity analyses remained within the World Health Organization's willingness-to-pay threshold, which is less than per-capita gross domestic product in Korea (about $25,700). Thus, we conclude that drug therapy for osteopenia would be a cost-effective intervention, and we recommend that the Korean National Health Insurance expand its coverage to include drug therapy for osteopenia.

* Abbreviations: AIR-P — : Autism Intervention Research Network on Physical Health ASD — : autism spectrum disorder CAA — : Combating Autism Act DBPNet — : Developmental-Behavioral Pediatrics Research Network HRSA — : Health Resources and Services Administration MCHB — : Maternal and Child Health Bureau In the United States, it is estimated that 1 in 68 children have autism spectrum disorder (ASD) according to data from the Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring Network.1 Based on data from the 2011–2012 National Survey of Children’s Health, a recent report suggests an even higher prevalence estimate of 1 in 50 children with ASD.2 These increasing prevalence data indicate that ASD continues to be a major public health concern in the United States requiring coordinated and collaborative efforts at the national, state, and community levels. Since 1995, the US Department of Health and Human Services has supported initiatives aimed at increasing our understanding of ASD, its causes, and potential treatments.3 These initiatives have paved the way to a more coordinated federal effort to address ASD and other developmental disabilities with the enactment of the Combating Autism Act of 2006 (CAA). This act authorized programs to address ASD and other developmental disabilities through research, screening, intervention, and education. Congressional appropriations included funding for the Health Resources and Services Administration (HRSA) to implement section 399BB of the CAA4 to address the following: 1. increase awareness of ASD and other developmental disabilities; 2. reduce barriers to screening and diagnosis; 3. support … Address correspondence to Hae Young Park, MPH, Maternal and Child Health Bureau, Health Resources and Services Administration, 5600 Fishers Ln, 18W51, Rockville, MD 20857. E-mail: hpark{at}hrsa.gov

Polypharmacy, regarded as an indicator of potentially inappropriate medications (PIMs), may lead to a higher risk of serious health consequences in elderly patients with osteoporosis. Thus, this study aimed to analyze the association between polypharmacy and hip fracture in patients with osteoporosis because only a limited number of studies have reported on this association, with inconsistent results to date. In this nested case–control study using a population-based sample cohort, the target cases were female patients with hip fracture diagnosed with osteoporosis and aged ≥ 50 years. Polypharmacy (prescription of an average of five or more daily drugs), PIMs for hip fracture (such as benzodiazepines and glucocorticoids), Charlson Comorbidity Index (CCI) score, and other comorbidities were analyzed during the year preceding the diagnosis of hip fracture. Adjusted odds ratios (ORs) for hip fracture for the variables were also analyzed. The cases (n = 1003) showed higher exposure rates to polypharmacy, glucocorticoids, and benzodiazepines, and had more severe comorbidity statuses compared with the controls. The ORs for hip fracture adjusted for confounders increased with polypharmacy level, with persistent statistical significance in most analyses. The ORs (95% confidence intervals), with reference to the 0 to

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A (α-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso‑Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso‑Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK‑2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso‑Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0‑fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial‑mesenchymal transition (EMT). The gene expression patterns of sphingolipid‑treated HK‑2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso‑Gb3. In the HK‑2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1, IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso‑Gb3 revealed substrate‑specific and cell‑specific patterns. These findings suggested that Gb3 and lyso‑Gb3 lead to renal fibrosis in Fabry disease through different biochemical modulations.

Whereas the incidence of visual impairment and blindness (VI&B) is decreasing, the total number of VI&B is increasing due to the growth of elderly population. To compare the clinical and economic outcomes of patients with and without VI&B (ie, cases and controls) in Korea, a case–control study was performed using the Health Insurance Review and Assessment Service–National Patients Sample data. Cases had higher prevalence for all of the Charlson Comorbidity Index components, depression, fracture, and injury as well as eye diseases compared to age- and sex-matched controls. In regression after adjustment of concomitant diseases, cases had 2.7 times (95% confidence interval = 2.3-3.2) higher medical expenditure than controls. The results of this study confirm that patients with VI&B have significantly higher direct medical expenditures and concomitant diseases than those without VI&B and highlight the need for a public health strategy to reduce potentially avoidable costs attributed to VI&B.

The response of B cells to Ag targeted to Clec9A on dendritic cells was followed using the hapten nitrophenol (NP) conjugated to rat Ig carrier. Injection of small amounts of NP conjugated to anti-Clec9A in the absence of adjuvants gave high and very prolonged Ab responses, approaching those obtained by high doses of nontargeted NP–protein conjugates with alum adjuvant. The response to NP–anti-Clec9A included the transient formation of germinal centers, maturation of Ab affinity, and some memory B cell formation. Serum Ab titers remained high 35 wk postimmunization, well after the initial follicular response had faded. The results suggest Clec9A-targeting strategies for improving Ab responses to vaccine Ags.

Riehl's melanosis presents as a diffuse gray-brown to black hyperpigmentation around face. The treatment of this disease is challenging and quite limited despite patients' excessive psychological stresses.In this prospective pilot study, we evaluated the efficacy and safety for a novel combination therapy based on low-fluence Q-switched 1064 nm Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl's melanosis.Totally eight patients with Riehl's melanosis who had failed improvements previously received multiple sessions (10-18 times) of combination treatment regimen. The primary endpoint was clinical score by the physician and the secondary endpoints were clinical score by the patients, instrumental analysis using melanin and erythema values, and histopathological score.Among eight patients, three received "Almost clear" grade, the other five patients received "Marked improvement" grade at final visits. No serious adverse events and post-treatment downtime was observed. Mean Melanin and Erythema Indexes also showed significant decreases compared with baseline. Histopathologic examination confirmed a significantly greater reduction of melanin content in melanophages.This combination method can be a viable option for Asian patients having Riehl's melanosis with high risk of post-inflammatory hyperpigmentation, maintaining low-dose laser irradiation.

OBJECTIVE This study was conducted to analyze and compare the exposure to individually prescribed drugs and the prevalence of polypharmacy according to age group and concomitant disease in South Korea. METHODS The use of prescribed drugs was evaluated according to average numbers of prescription drugs used daily during a year or month, using the Korean Health Insurance Claims Database, which is representative of over 90% of citizens, in 2010 and 2011. The use of prescribed drugs was also analyzed according to concomitant diseases and age. Polypharmacy was defined as the use of 5 or more drugs daily during a specific observation period, and proportions of polypharmacy users were calculated according to comorbidity and age group. RESULTS The annual average numbers of daily used prescription drugs in 2010 and 2011 were 0.3 (SD = 0.5), 0.4 (SD = 0.7), 1.2 (SD = 1.5), and 2.3 (SD = 2.0) for people aged < 20 years, 20-49 years, 50-64 years, and ≥ 65 years, respectively. Proportions of individuals demonstrating polypharmacy increased with age and were 9.5% and 44.1% for elderly individuals in the year- and month-based analyses, respectively. The annual average number of daily medications used increased by ~2 drugs in the concomitant disease group, and the higher mortality group used a higher number of prescribed drugs than the lower mortality group. CONCLUSIONS The results highlight the elevated burden of multi-medication in elderly patients, and the study found that prescribed drug use increased with age and the number of concomitant diseases.

Although periorbital edema is a common manifestation of dermatomyositis (DM), generalized subcutaneous edema associated with DM is extremely rare. Evans syndrome is an autoimmune disease in which an individual's antibodies attack one's own red blood cells and platelets. Evans syndrome is rarely a presenting feature of DM. DM has been rarely reported to be associated with either generalized edema or Evans syndrome. We report the case of a 52-year-old Korean woman who presented with generalized subcutaneous edema, an erythematous rash, dysphagia, and proximal muscle weakness, and subsequently developed features of Evans syndrome. Treatment with high-dose glucocorticoids and an immunosuppressive agent controlled the DM, the generalized subcutaneous edema, and the Evans syndrome.

Purpose The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. Materials and methods We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. Results p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. Conclusion S: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer.

Purpose : The purpose of this study was to compare the effects of different supporting surfaces on trunk muscle activities during core stabilization exercises. Methods : A total of 20 healthy college students participated in this study for 6 weeks. In this study, we divided participants into a stable surface exercise group and an unstable surface exercise group. Each group performed core stabilization exercises of Curl-ups, Bridges, and Quadrupedal position. Core stabilization exercises were performed 3 times a week for 30 minutes during 6 weeks. The stable surface exercise group used a yoga mat while the unstable surface exercise group used AERO step. This study was designed using pre-test and post-test measurements. We used Surface Electromyograpy (sEMG) to measure for the rectus abdominis, external abdominal oblique, and multifidus muscle of trunk muscle activities. Data was processed using a paired sample t-test on SPSS 18.0. Results : For the stable surface exercise group there was a meaningful improvement in left rectus abdominis, left external abdominal oblique, and right multifidus (p

The her2 messenger RNA (mRNA) was the most abundant among the erb type-1 tyrosine kinase receptors mRNA in human testis and was statistically significantly decreased in impaired spermatogenesis. Testicular HER2 was tyrosine phosphorylated and strongly expressed in spermatogonia, early spermatocytes, elongating/elongated spermatids, Sertoli cells, Leydig cells, and peritubular cells, suggesting that activated HER2 participates in mitosis and meiotic entry of germ cells, spermiogenesis, and steroidogenesis via mediating the epidermal growth factor–growth factor signaling.

Background Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.

The purpose of this study is to weigh the students' backpacks of middle school in daily use and to analyse their physiological responses and subjective senses when carrying backpack in order to promote healthy and comfort school life of girl middle school students. Two female students were subjects who answered the questionnaires on two types of backpack and their metabolism, perspiration and the changes of skin temperature were measured in constant environment chamber, 25±1 and 49±10% RH. They walked on the treadmill carrying the backpack with the increment of backpack weight, 2 kg, 4 kg to 6 kg. When the backpack increases to 6 kg, the discomfort parameters and responses increases rap- idly. Comparing with general type, improved type of backpack showed good results in physiological responses, but not in subjective senses, such as the ease of movement, pain, or total preference, specially in 2 kg and 4 kg. The girl students prefer the general type of backpack which is of fashion and small, when it weighs light such as 2 kg or 4 kg, while they prefer the improved bag which is functional when it is heavy as 6 kg. The longer wearing time of the medium weight, for example, 4 kg without feeling or recognition of any discomfort due to fashion style, might cause the students' posture and health weaker or more vulnerable to the problems.

This study investigated whether endoplasmic reticulum (ER) stress induced retinal ganglion cell (RGC) death in chronic ocular hypertension, one of the RGC death mechanisms, using an experimental glaucoma rat model. Glaucoma was induced in adult male Sprague-Dawley rats by cauterizing three episcleral veins. The intraocular pressure (IOP) remained elevated in the cauterized eyes for the 8-week experiment, whereas it was not elevated in the contralateral control eyes. The average number of RGCs decreased significantly, and TUNEL-positive cells were detected in the ganglion cell layer. In western blotting, Bip, the phosphorylated form of PKR (p-PERK), and C/EBP-homologous protein (CHOP) were significantly expressed at 1 or 2 weeks, and this persisted throughout the 8-week experiment. Phosphorylated eukaryotic initiation factor 2 (p-eIF2alpha) began to increase at 1 week, was sustained through 4 weeks, and decreased slightly at 8 weeks. In cauterized eyes, strong p-PERK and CHOP immunoreactivity was observed in ganglion cells after 8 weeks of IOP elevation. Taken together, in the experimental chronic glaucoma model, ER stress is involved in RGC death, and the PERK-p-eIF2alpha-CHOP pathway plays a role in the RGC apoptosis associated with ER stress. This might be a good therapeutic target to protect RGCs from ER stress injury in glaucoma.

Neutrophils are also known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. In this study, neutrophils were cultivated in vitro in the presence or absence of compounds modulating their survival in an attempt to characterize the expression profile of the DC markers. Higher MHC-II, CD80, CD86, CD83, and CD40 expression levels were detected on the surface of the cultured neutrophils for 24 h than on the freshly isolated cells. The annexin V-positive cells showed a higher expression level of the DC markers than the annexin V-negative cells. The population of neutrophils double stained with annexin V and the DC markers increased after being incubated with agonistic anti-Fas Ab. LPS, the anti-apoptotic compound, decreased the CD86 and MHC-II expression levels but 50-60% of the DC marker-positive cells were detected in the annexin V-positive cells. In contrast, CD80, CD86, CD83, and HLA-DR mRNA levels increased in the GM-CSF-treated neutrophils but not in the anti-Fas Ab-treated neutrophils. T cell proliferation was inhibited by co-culturing them with anti-Fas Ab- or LPS-treated neutrophils at a high neutrophil:T cell ratio. However, the superantigen-mediated T cell proliferation was increased by the LPS-treated neutrophils but decreased by the anti-Fas Ab-treated neutrophils. There was a lower level of interferon-gamma production in the T cells co-cultured with anti-Fas Ab-treated neutrophils than with the LPS-treated neutrophils. This suggests that apoptotic neutrophils express DC markers on their surface and the differential expression of DC markers might have a detrimental effect on the immune reaction.

Purpose Bedaquiline is a new drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). This study aimed to evaluate the cost-effectiveness of adding bedaquiline to a standard regimen (SR) for treating patients with MDR-TB, including extensively drug-resistant (XDR)-TB, in the Republic of Korea. Methods A cohort-based decision-analytic model developed in a previously published study from the United Kingdom was used, with a 20-year time horizon and a 5% discount rate for cost and effectiveness, to evaluate the incremental cost-effectiveness ratios of bedaquiline + SR and SR only. The key parameters regarding the clinical data were available via the published Phase II trial of bedaquiline. Additional parameters for recurrence, cure status, loss to follow-up, surgery, death, cost, and health utility were based on Korean data if available; otherwise the international literature data were applied. Univariate and probabilistic sensitivity analyses were conducted. Findings Based on the analysis, a patient on bedaquiline + SR would gain 1.20 quality-adjusted life-years (QALYs) at 13,961,659 Korean won (KRW) (1100 KRW = US $1) of additional cost compared with a patient administered SR only, with an incremental cost/utility ratio of 11,638,656 KRW/QALY. Bedaquiline + SR had an 80% probability of being cost-effective, at a willingness-to-pay threshold of 26 million KRW, compared with SR only. Implications The results of this study suggest that, in the Republic of Korea, bedaquiline, as a part of combination therapy with SR, is a cost-effective option for the treatment of MDR-TB (including XDR-TB) compared with SR only.

A high-performance liquid chromatographic method was employed for the determination of bumetanide in human plasma. After addition of internal standard (IS, naproxen) and acidification of the plasma with 1 M hydrochloric acid, the drug and IS were extracted into dichloromethane. The organic phase was back-extracted into 1 M sodium bicarbonate solution and 50 of the aqueous phase was injected onto a reversed-phase C18 column with a mobile phase consisting of methanol: water: glacial acetic acid = 65 : 35 : 1. The samples were detected utilizing a fluorescence detector (excitation wavelength 235 nm, emission wavelength 405 nm). The method was specific and validated with a lower limit of 5 ng/mL. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of the method was demonstrated by analysis of plasma after oral administration of a single 2 mg dose to 24 healthy subjects. From the plasma bumetanide concentration vs. time curves, the mean AUC was and of ng/mL reached 1.2 hr after administration. The mean biological half-life of burnet ani de was hr. Based on the results, this simple and validated assay method could readily be used in any pharmacokinetic or bioequivalence studies using humans.

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for naive T cells and play an important role in cancer immunology. All-trans retinoic acid (ATRA) is known to be a differentiating agent in the treatment of acute promyelocytic leukemia (APL). In this study, we investigated whether ATRA can differentiate the retinoic acid (RA)-sensitive promyelocytic leukemic cell line, NB4, to DC-like cells and whether these differentiated cells can activate T cells. NB4 cells were differentiated to myeloid cells by 4, 6, and 8 days of ATRA treatment. NB4 cells up-regulated markers found in DCs, including HLA-DR, costimulatory molecules (CD80 and CD86), adhesion molecules (CD40), and chemokine receptors (CCR6) when cultured for 8 days in the presence of 1 microM ATRA. Upregulation of CD83 was also detected on the surface of ATRA-treated NB4 cells versus untreated cells. The addition of cytokines alone, such as GM-CSF or CD40 ligand, did not affect the expression of CD83 in untreated NB4 cells but they up-regulated CD83 in ATRA-treated cells. CD11b was coexpressed with CD80, CD83, and CD86 in ATRA-treated NB4 cells. In a functional assay, ATRA-treated NB4 cells stimulated T cell proliferation when challenged with Staphylococcus enterotoxin B. These results suggest that the differentiation of NB4 cells by ATRA causes the cells to express DC markers, and that ATRA-differentiated NB4 cells are able to present antigens to T cells.

Summary. Natural killer T (NKT) cells are involved in innate immune defence and also in the regulation of adaptive immune responses. However, the development of NKT cells in vitro has not been fully characterized and culture conditions have not been fully optimized. In the present study, we found that an NKT cell fraction developed during the in vitro culture of cord blood (CB) CD34+ cells, and this was subsequently characterized both phenotypically and morphologically. CD34+ cells purified from 10 human CB were cultured in the presence of several cytokines and analysed by flow cytometry, light microscopy and electron microscopy. The NKT cell fraction, defined phenotypically (CD3+CD16+CD56+CD94+) as expressing the invariant T-cell receptor Vα24 and Vβ11, appeared in the CD56hi fractions. Intracytoplasmic staining demonstrated that interferon-γ and interleukin 4 (IL-4) were detected in the CD56hi fractions. IL-15 was essential and, in combination with either flt3-ligand (FL) or stem cell factor (SCF), was sufficient to induce the development of NKT cells. The phenotype of the NKT cell fraction was CD45RO+CD45RA– and CD4+CD8α+. Morphologically, they were very large, with either round or oval nuclei, moderately condensed chromatins, voluminous weakly basophilic cytoplasm and various cytoplasmic granules such as dense core granules, multivesicular bodies, and intermediate form granules. When CD34+ cells purified from bone marrow (BM) were compared with those from CB, the latter were consistently more efficient at generating CD56hi NKT cell fractions. In conclusion, IL-15 in combination with FL and/or SCF can induce the differentiation of NKT cells from human CB CD34+ cells.

Acute generalized exanthematous pustulosis (AGEP) is manifested by rapid development of many sterile, nonfollicular pustules on a background of edematous erythema. More than 90 percent of AGEP are induced by medication, mostly antibiotics. Drug patch test can be helpful in the diagnosis of AGEP. This paper reports the first case of celecoxib-induced AGEP confirmed by patch test in Korean literature.

Objectives. The cadherin/catenin adhesion complex is fundamentally involved in epithelial cancer invasion and metastasis. Much evidence suggesting that epidermal growth factor (EGF) induced the scattering and invasion of cancer cells, probably by affecting E-cadherin function, has been reported. The present study aimed to confirm the hypothesis that EGF/epidermal growth factor receptor (EGFR) was related with the E-cadherin adhesion system in cervical cancer cells and that EGF might induce tyrosine phosphorylation of β- and γ-catenin. Methods. Cervical cancer cells were treated for different time durations with 30 ng/ml of EGF. Alteration of the cell morphology was examined by light microscopy and the expression of E-cadherin, β-catenin, γ-catenin, EGFR, and activated EGFR was assayed using Western blotting. Tyrosine phosphorylation of β- and γ-catenin was also examined using immunoprecipitation. Results. E-cadherin and EGFR were expressed in CaSki, HT-3, and ME-180 cell lines, which showed epithelial contact growth. The expression of E-cadherin and β- and γ-catenin did not change after treatment with EGF. The expression of EGFR decreased and activated EGFR expression increased in 30 min and then decreased subsequently. The simultaneous expression of activated EGFR and tyrosine phosphorylation of β- and γ-catenin was found. Conclusions. EGF-induced scattering of the E-cadherin-positive cervical cancer cells might be the result of tyrosine phosphorylation of the β- and γ-catenin. Phosphorylation of the β- and γ-catenin may hamper the adhesive function of the E-cadherin–catenin complex.

We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

Eleven lignans (1–11) were isolated from the CH2Cl2 fraction of the bark of Machilus thunbergii Sieb, et Zucc. (Lauraceae). These were identified as (-)-acuminatin (1), (-)-isoguaiacin (2), meso-dihydroguaiaretic acid (3), (+)-galbacin (4), (-)-sesamin (5), (+)-galbelgin (6), machilin A (7), machilin G (8), licarin A (9), and nectandrin A (10) and B (11). Primary cultures of rat hepatocytes were co-incubated for 90 min with the hepatotoxin CCl4 and each of the 11 lignans (50 μM). Hepatoprotective activity was determined by measuring the level of glutamic pyruvic transaminase released into the medium from the primary cultures of rat hepatocytes. (-)-Acuminatin, (-)-isoguaiacin and meso-dihy-droguaiaretic acid all significantly reduced the level of glutamic pyruvic transaminase released. Further investigation revealed that these three compounds significantly preserved the levels and the activities of glutathione, superoxide dismutase, glutathione peroxidase and catalase. (-)-Acuminatin, (-)-isoguaiacin and meso-dihydroguaiaretic acid also ameliorated lipid peroxidation as demonstrated by a reduction of malondialdehyde production. These results suggest that (-)-acuminatin, (-)-isoguaiacin and meso-dihydroguaiaretic acid exert diverse hepatoprotective activities, perhaps by serving as potent antioxidants.

In order to study the simultaneous determination of (+)- and (-)-cetirizine in human urine we have developed a chiral separation method by HPLC. A chiral stationary phase of alpha1-acidglycoprotein, the AGP-CSP, was used to separate the enantiomers. The pH of the phosphate buffer, as well as the content of the organic modifier in the mobile phase, markedly affected the chromatographic separation of (+)- and (-)-cetirizine. A mobile phase of 10 mmol/l phosphate buffer (pH 7.0)-acetonitrile (95: 5, v/v) was used for the urine assays. Ultraviolet absorption was monitored at 230 nm and roxatidine was employed as the internal standard for quantification. (+)-Cetirizine, (-)-cetirizine and the internal standard were eluted at retention times of 12, 16, and 32 mins, respectively. The detection limit for cetirizine enantiomers was 400 ng/ml of urine. A pharmacokinetic study was conducted with the help of 5 healthy female volunteers who were administered with a single oral dose of racemic cetirizine (20 mg). The peak area ratios provided by the cetirizine enantiomers were linear (r0.997) over a concentration range of 2.5-200 microg/ml. The peak of the excreted cetirizine enantiomers appeared in the urine sample during the period of 1-2 hrs following the administration of the oral dose. The excreted level of (+)-cetirizine was slightly higher than (-)-cetirizine but the difference was not statistically significant. However, this method appears to have applications for enantioselective pharmacokinetic studies of racemic drugs.

The relationship between the metabolites of glycyrrhizin (18beta-glycyrrhetinic acid-3-O-beta-D-glucuronopyranosyl-(1-->2)-beta-D-glucuronide, GL) and their biological activities was investigated. By human intestinal microflora, GL was metabolized to 18beta-glycyrrhetinic acid (GA) as a main product and to 18beta-glycyrrhetinic acid-3-O-beta-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.

We investigated the phenotypic changes of human umbilical cord blood (CB) CD34+ cells during ex vivo expansion using thrombopoietin (TPO), flt3-ligand (FL), and/or granulocyte-colony stimulating factor (G-CSF). During ex vivo expansion of CD34+ cells isolated from human CB for up to 5 weeks, surface expression of molecules on the cultured cells including CD64 (FcγRI), CD32 (FcγRII), CD16 (FcγRIII), CD11b (MAC-1) and CD18 (β2-integrin) was analysed by flow cytometry along with simultaneous measurement of apoptosis by 7-aminoactinomycin D staining method. CD64, CD32 and/or CD18 expressing cells appeared in the cultures both with and without the addition of G-CSF until the tenth day. However, without G-CSF, CD16+ fractions did not appear and CD11b+ fractions were not maintained. With G-CSF, the CD16+ or CD11b+ fractions appeared only from the second week. These results suggest that G-CSF is necessary for the late stage of myeloid maturation during which CD16 and CD11b are expressed.

We investigated the Bcl-2 and P53 protein expressions in 89 patients with bladder cancers using immunohistochemical analysis. In superficial tumors, the times of tumor recurrence and progression were significantly shorter in the P53-positive group than in the negative group (p < 0.005, p < 0.05, respectively). In invasive tumors, the disease-specific actuarial survivals were significantly lower in the P53 and Bcl-2-positive groups (p

In search of critical genes associated with the mechanism of transforming growth factor-alpha (TGF alpha) action in human ovarian cancer, it was found that TGF alpha stimulates c-myc gene expression in human ovarian NIH:OVCAR-3. The role of c-myc in TGF alpha-stimulated growth of NIH:OVCAR-3 cells was examined by the use of the synthetic antisense-myc phosphorothioate oligonucleotide (OPT). Prior exposure of NIH:OVCAR-3 cells to an antisense-myc OPT inhibited TGF alpha-stimulated cell growth and DNA synthesis in a dose-dependent and sequence-specific manner over 4 days. c-Myc protein expression was down-regulated in the antisense-myc treated cells. These results demonstrate both the specific and durable effects of the antisense-myc OPT. Furthermore, the results suggest a role for c-myc in TGF alpha-stimulated cell proliferation.

* Abbreviations: ASD — : autism spectrum disorder CAAI — : Combating Autism Act Initiative DBP — : Developmental Behavioral Pediatrics HRSA — : Health Resources and Services Administration MCH — : Maternal and Child Health MCHB — : Maternal and Child Health Bureau SDAS — : Secondary Data Analysis Studies Over the past 2 decades, autism has emerged as a major public health concern in the United States.1 Since 1995, the US Department of Health and Human Services has sharpened its focus on autism spectrum disorders (ASDs) through development of new initiatives that are aimed at increasing our understanding of autism, its causes, and potential treatments.2 However, families and young children with ASD and other related developmental disabilities continue to face many challenges in health care and educational service system access, ensuring optimal development through early intervention, a successful transition into adulthood, and fostering family well-being and positive family functioning in diverse racial and ethnic populations. To further address autism as a critical and growing public health concern, Congress enacted the Combating Autism Act of 20063 in December 2006, which authorized programs to combat autism through research, screening, intervention, and education. As stated in this legislation, the Secretary of Health and Human Services shall “establish and evaluate activities to: 1. provide information and education on autism spectrum disorder and other developmental disabilities to increase public awareness of developmental milestones; 2. promote research into the development and validation of reliable screening tools for autism spectrum disorder and other developmental disabilities and disseminate information regarding those screening tools; 3. promote early screening of individuals at higher risk for autism spectrum disorder and other developmental disabilities as early as practicable, given evidence-based screening techniques and interventions; 4. increase the number of individuals who are able to confirm or rule out a diagnosis of autism spectrum … Address correspondence to Hae Young Park, MPH, Health Resources and Services Administration, Maternal and Child Health Bureau, 5600 Fishers Lane, 18A-55, Rockville, MD 20857. E-mail: hpark{at}hrsa.gov

Dear Editor: A 52-year-old male diagnosed with metastatic melanoma began treatment with 400 mg oral imatinib daily. The only other significant medical condition was a 20-year history of mild psoriasis, which was well-controlled with intermittent topical corticosteroid and calcipotriol ointment. The patient's pre-existing psoriasis did not require treatment for about two months before imatinib treatment was initiated. After two months of imatinib therapy, he presented with a painful, symmetric erythema on the palms and soles without any history of contact with irritants (Fig. 1A). Physical examination demonstrated the patient also developed not only palm and sole lesions but also erythematous, scaly papules to plaques of various sizes on the buttocks (Fig. 1B). He presented simultaneously with nail crumbling, pitting, onycholysis, beau lines, and subungual hyperkeratosis, which are typical features of psoriatic nail dystrophy (Fig. 1C). The patient had never experienced nail changes or any symptom of paronychia prior to this incident. For the painful palms and soles, hand-foot syndrome was diagnosed based on his clinical presentation. Since then, imatinib was discontinued and both palms and soles were treated with a short course of potent topical steroids. For the buttock lesions, a skin biopsy was performed. Fig. 1 (A) After two months of imatinib treatment, the patient developed painful symmetric erythema over palms and soles and desquamation with pain. (B) Exacerbation of guttate psoriasis on the buttocks after two months of imatinib treatment. (C) The patient ... Two weeks later, the patients visit our clinics to check the result of biopsy, which suggested the exacerbation of underlying psoriasis (Fig. 2). Although palms and soles showed improvement, his buttock lesion kept aggravating when he visited the clinics. We then started topical corticosteroid and calcipotriol ointment. The withdrawal of imatinib treatment and application of topical corticosteroid and calcipotriol ointment gradually improved psoriatic skin lesions, and his skin condition was almost fully resolved after six weeks, but the nail changes have persisted (Fig. 1D). Imatinib administration was then re-initiated at the reduced dose of 200 mg daily; the skin lesions remain well-controlled. Fig. 2 Histopathologic examination of a biopsy from the buttocks shows epidermal hyperkeratosis, loss of granular layer, regular acanthosis with parakeratosis, and microabscess (H&E, ×100). Imatinib mesylate is a small-molecule compound that selectively inhibits multiple tyrosine kinases, including bcr-abl, c-kit, and platelet-derived growth factor receptor. Various cutaneous adverse reactions including nonspecific erythematous maculopapular rash, pityriasis rosea-like eruptions, and psoriasiform eruptions, have been reported1. In a review of published work, we found that there are several reports that imatinib may affect the pathogenesis of psoriasis. In most patients, psoriatic skin lesions occurred one to five months after 400 mg imatinib daily and improved upon withdrawal of imatinib and treatment with narrow-band ultraviolet B therapy. Topical corticosteroids with vitamin D analogues also facilitated improvement. After skin lesions resolved, dasatinib or nilotinib, a second-generation tyrosine kinase inhibitor, could be administered instead of imatinib Actually, second-generation tyrosine kinase was administered instead in two cases; subsequent psoriatic lesions were not reported2,3. The mechanism behind imatinib-mediated psoriasis remains unknown. Woo et al.2 suggests a dose-dependent relationship, as his patient experienced exacerbation of underlying psoriasis after the imatinib dose was increased from 200 mg/day to 400 mg/day. The observed association between dose and psoriasis suggests that the immunological disturbance of psoriasis may be related to a pharmacological effect of imatinib. Previous studies showed that imatinib can block signaling pathways in regulatory T cells; further, the T-cell receptor may be blocked by imatinib due to inhibition of the phosphorylation of leucocyte-protein tyrosine kinase and reduced intracellular signaling in effector T cells4,5. Based on these results, Thachil5 proposed that "the balance between the regulatory and effector function of T cell" may determine the outcome of psoriasis; imatinib has been shown to interfere with this balance by blocking intracellular signaling. The dose-dependent characteristics in this case suggest that pharmacological effects of imatinib play a pathological role in psoriasis. Further studies are needed to elucidate the precise mechanism by which imatinib induces this adverse cutaneous effect.