Search

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.

a parametric investigation was conducted to evaluate the effect of the laser beam for plastic adhesion. To determine the best condition for plastic adhesion, the co₂ (wavelength 10.6㎛) and nd:yag (wavelength 1.06 ㎛) laser were experimented with. From the experiment results obtained, the nd:yag laser was revealed to be the most suitable for plastic adhesion. In this study, three adhesion parameters such as input power level, working time of laser beam and pps (pulse per second) were systematically adjusted for suitable adhesion. From these experiments, it was observed that the target plastic melted and was evaporated by the nd:yag laser. Furthermore, the relationships between adhesive surface by laser beam and above three parameters were discovered.

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.

This study examined the effect of amyloid beta peptide (Abeta) and the secretase inhibitors of amyloid precursor proteins (APP) on the spontaneous apoptosis of neutrophils. Abeta(1-40) decreased the apoptotic rate of neutrophils. The delayed apoptosis by Abeta was not blocked by pertussis toxin and N-formyl peptide receptor-like 1 antagonistic peptide, WRWWWW. The inhibitors of phoshoinositide 3-kinase (LY294002), phospholipase C (U73122), or Ca++-dependent protein kinase C (Go6976) abrogated the anti-apoptotic effect of Abeta on neutrophils. Moreover, the Abeta-induced delay of apoptosis was inhibited by a calcium chelator, BAPTA/AM. The amount of the APP protein was reduced in the cultured neutrophils and the APP level in the Abeta or pancaspase-treated neutrophils was lower than that in the cultured neutrophils. However, the reduction in APP level was recovered after treating them with the secretase inhibitors or anti-Fas antibody. The exogenous addition of cell permeable beta- and gamma-secretase inhibitors resulted in an increase in the rate of the apoptosis. The regulation of neutrophil apoptosis by the addition of Abeta and secretase inhibitors occurred via the caspase -8, -9, -3, and mitochondrial-dependent pathways. This suggests that the intracellular beta-amyloid proteins play a role as regulating factor of neutrophil survival and that Abeta-induced delay of apoptosis is mediated by other receptors rather than a seven-transmembrane G protein-coupled receptor(s).

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.

Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by signals triggered by various stimuli. In this work, we investigated the action mechanism of phospholipase D (PLD) and its expression in the inhibition of spontaneous and Fas-mediated apoptosis. Anti-Fas antibody-stimulated apoptosis of neutrophils was significantly blocked by the exogenous addition of bacterial PLD from Streptomyces chromofuscus (scPLD), and neutrophils cultured for 24 h in the presence of anti-Fas antibody showed lower agonist-stimulated PLD activity compared to untreated cells. The amount of PLD1a protein reduced time-dependently in cultured neutrophils, but was recovered by treating with LPS or GM-CSF. The reduction in PLD1a protein level was blocked by caspase inhibitors. The exogenous addition of scPLD blocked the up-regulation of Fas-associated death domain expression, mitochondrial permeability, and the cleavages of procaspase-8, procaspase-3, and protein kinase C-delta. We also found that the protein level of apoptosis-inducing factor was increased in cultured neutrophils but its expression was reduced by scPLD. However, sulfasalazine-induced apoptosis and change of protein expression were not blocked by scPLD. Taken together, the activity and protein levels of PLD play a role as an anti-apoptotic factor by acting at multiple levels of the apoptotic cascade in neutrophils.

Agents that elevate cellular cAMP are known to inhibit the activation of phospholipase D (PLD). We investigated whether PLD can be phosphorylated by cAMP-dependent protein kinase (PKA) and PKA-mediated phosphorylation affects the interaction between PLD and RhoA, a membrane regulator of PLD. PLD1, but not PLD2 was found to be phosphorylated in vivo by the treatment of dibutyryl cAMP (dbcAMP) and in vitro by PKA. PKA inhibitor (KT5720) abolished the dbcAMP-induced phosphorylation of PLD1, but dibutyryl cGMP (dbcGMP) failed to phosphorylate PLD1. The association between PLD1 and Val14RhoA in an immunoprecipitation assay was abolished by both dbcAMP and dbcGMP. Moreover, RhoA but not PLD1 was dissociated from the membrane to the cytosolic fraction in dbcAMP-treated cells. These results suggest that both PLD1 and RhoA are phosphorylated by PKA and the interaction between PLD1 and RhoA is inhibited by the phosphorylation of RhoA rather than by the phosphorylation of PLD1.

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.

Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.

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.

The insufficient number of haemopoietic stem cells (HSCs) in cord blood (CB) is the major potential limitation to widespread use of CB for marrow replacement. Cytokine-mediated ex vivo expansion has been proposed as a means of increasing the number of CB HSCs for transplantation. However, the biology of CB HSCs during cytokine-mediated ex vivo expansion, such as apoptosis or expression of adhesion molecules, has not yet been elucidated. We have investigated the patterns of apoptosis and CD44 expression on human CB CD34+ cells during ex vivo expansion. CD34+ cells isolated from human CB were cultured in a stroma-free liquid culture system with thrombopoietin (TPO), flt3-ligand (FL), stem cell factor (SCF), and/or granulocyte-colony stimulating factor (G-CSF). During the culture, for up to 5 weeks, apoptosis was measured by staining with 7-amino-actinomycin D (7-AAD) along with concurrent immunophenotyping of CD34 and CD44 with three-colour flow cytometry. In the cultures with TPO, an apoptotic fraction with down-regulated CD44 appeared from the fourth day up to the second week. G-CSF also induced apoptosis but in a different manner; the apoptotic fraction without down-regulation of CD44 appeared unremittingly for up to 5 weeks. FL did not induce apoptosis or down-regulation of CD44. These findings show that apoptosis is indeed involved in the regulation of CB CD34+ cells in ex vivo expansion and the patterns of apoptosis are dependent on the type of cytokines used. The distinct patterns of apoptosis suggest different mechanisms of TPO and G-CSF in inducing apoptosis, which still remains to be elucidated.

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

To investigate whether transforming growth factor α (TGF α) treatment of human ovarian cancer cells was associated with the induction of c-myc protooncogene, the expression of this gene in NIH:OVCAR-3 cells was examined. TGF α induced increase in c-myc mRNA level, with a peak after 1 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 5 ng/ml TGF α. Its primary action is probably at the transcription level since the half-life of c-myc mRNA measured in the presence of actinomycin D was not modified by TGF α treatment. In addition, TGF α stimulation of c-myc mRNA did not require protein synthesis since it was not suppressed by cycloheximide treatment. Antisense phosphorothioate oligonucleotide to c-myc specifically inhibited the TGF α-stimulated c-Myc protein expression and growth of NIH:OVCAR-3 cells. Our results indicate that induction of c-myc expression by TGF α plays an important role in the growth of NIH:OVCAR-3 cells.

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.

The expression of cytochrome P450 genes directly within target cells is an important determinant of human susceptibility to cancers and other chemically initiated diseases. One pivotal gene, C Y P 1 A 1 codes for an inducible cytochrome P450 isozyme 1A1 responsible for the bioactivation of numerous carcinogenic polycyclic hydrocarbons. In the present study, the effects of 3-methylcholanthrene, a polycyclic aromatic hydrocarbon, on the activity and expression of CYP1A1 and the protective effects of diallyl sulfide on 3-methylcholanthrene-induced changes in mice liver and lung were investigated. After a four daily 3-methylcholanthrene-treatment (25 mg/kg, i.p.), liver and lung microsomal 7-ethoxyresorufin-Odeethylase (EROD) activity, associated with CYP1A1, was increased. A corresponding increase in the level of CYP1A1 mRNA was observed in mouse liver and lung after 3-methylcholanthrenetreatment by Northern blot analysis. Diallyl sulfide reduced 3-methylcholanthrene-induced CYP1A1 mRNA expression and its associated EROD activity in mouse liver and lung. The modulation of CYP1A1 mRNA by 3-methylcholanthrene and diallyl sulfide was mainly due to transcriptional regulation.

* 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.

Background: Staphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients. Objective: We sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA. Methods: We evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea). Results: The SA colonization rates were 74%, 38% and 3% in acute, chronic skin lesions and control skin, respectively, and they were increased with age in AD patients. The colonization rate in chronic skin lesions was higher in the high IgE/eosinophilia groups as compared to the normal IgE/eosinophil groups. Conclusion: The SA colonization rate was higher in AD patients and especially in acute lesions, and had a tendency to increase with age. As the colonization rates were only higher in the high IgE/eosinophilia groups of chronic skin lesions, we suggested that SA may invade the skin through barrier defects in acute skin lesions, but the colonization in chronic lesions may be orchestrated through many different factors. (Ann Dermatol 25(4) 410∼416, 2013)

Purpose: Bladder wall thickness (BWT) is reported to be related to detrusor overactivity and bladder outlet obstruction. We investigated the relationship between BWT and the responsiveness of storage symptoms to alpha-blockers in men with lower urinary tract symptoms (LUTS). Materials and Methods: A total of 74 patients with LUTS were enrolled. International Prostate Symptom Score, uroflowmetry with post-void residual urine volume, and transrectal ultrasonography (TRUS) were investigated. BWT was measured by performing TRUS at the midsagittal plane view, and the average value of BWT at the anterior, dome, and trigone areas was used. After 4 weeks of alpha-blocker medication, patients were reevaluated and divided into two groups. The responder group consisted of patients who reported improvement in the storage symptom subscore of 2 points or more; the non-responder group consisted of patients who reported improvement of less than 2 points. Clinical parameters including BWT were compared between the two groups. Results: A total of 52 patients were followed. BWT was positively correlated with intravesical prostate protrusion (IPP) (9.26±4.99, standardized beta=0.393, p=0.002) and storage symptom subscore (0.35±0.43, standardized beta=0.458, p=0.002). Compared with that in the responder group, BWT was thicker in the non-responder group, and improvement in the storage symptom score was correlated with BWT (0.58±0.09 cm vs. 0.65±0.11 cm, p=0.018) and prostate volume (27.08±16.26 ml vs. 36.44±10.1 ml, p=0.018). Conclusions: BWT was correlated with IPP, the storage symptom subscore, and the responsiveness of storage symptoms to alpha-blockers in LUTS/benign prostatic hyperplasia (BPH) patients. As BWT increased, the responsiveness of storage symptoms to alpha-blocker decreased in LUTS/BPH patients.

PURPOSE We analyzed the prescriptions of alpha-blockers and phosphodiesterase 5 inhibitors (PDE5Is) in the urology department as well as in other departments of the general hospital. METHODS We investigated the frequency of prescription of alpha-blockers and PDE5Is from 3 general hospitals from January 1, 2007 to December 31, 2009. For alpha-blockers, data were collected from patients to whom alpha-blockers were prescribed from among patients recorded as having benign prostatic hyperplasia according to the 5th Korean Standard Classification of Diseases. For PDE5Is, data were collected from patients to whom PDE5Is were prescribed by the urology department and by other departments. Alpha-blockers were classified into tamsulosin, alfuzosin, doxazosin, and terazosin, whereas PDE5Is were classified into sildenafil, tadalafil, vardenafil, udenafil, and mirodenafil. RESULTS Alpha-blockers were prescribed to 11,436 patients in total over 3 years, and the total frequency of prescriptions was 68,565. Among other departments, the nephrology department had the highest frequency of prescription of 3,225 (4.7%), followed by the cardiology (3,101, 4.5%), neurology (2,576, 3.8%), endocrinology (2,400, 3.5%), pulmonology (1,102, 1.6%), and family medicine (915, 1.3%) departments in order. PDE5Is were prescribed to 2,854 patients in total over 3 years, and the total frequency of prescriptions was 10,558. The prescription frequency from the urology department was 4,900 (46.4%). Among other departments, the endocrinology department showed the highest prescription frequency of 3,488 (33.0%), followed by the neurology (542, 5.1%), cardiology (467, 4.4%), and family medicine (407, 3.9%) departments in order. CONCLUSIONS A high percentage of prescriptions of alpha-blockers and PDE5Is were from other departments. For more specialized medical care by urologists is required in the treatment of lower urinary tract symptoms and erectile dysfunction.

This paper deals with a combined system with fuel cell and supercapacitor to provide a power to grid or electrical load. The supercapacitor is used to compensate the slow response of the fuel cell at the instant of abrupt load change. The operation of the bidirectional DC/DC converter for a supercapacitor during charging and discharging is analyzed, and a power control method to maintain a DC link voltage constant is proposed. Simulation results for 3kW combined system show the usefulness of the proposed method.

Thyroid hormone (T3) receptors (T3Rs) regulate transcription by binding to T3 response elements (TREs) located within promoter regions of T3-regulated genes. In rat pituitary GH4C1 cells, expression of a reporter containing herpes simplex virus thymidine kinase (TK) gene sequences (-105/+51) linked to the chloramphenicol acetyltransferase gene was stimulated 4- to 5-fold by T3. Linker scanning mutants of the TK promoter revealed that regions around -80 containing a CTF/NF-1 recognition sequence and around -10 are both required for regulation by T3. Endogenous T3Rs from GH4C1 cells labeled with [125I]T3 bound only to TK promoter DNA fragments containing the -10 region. The -22/-2 sequence (TK-TRE) contains half-sites oriented as an inverted repeat separated by 6 basepairs that are identical to and similar to an optimized TRE half-site. Purified chicken T3R alpha 1 forms apparent monomeric and dimeric complexes on the 32P-labeled TK-TRE, as found previously with an inverted repeat of the optimized TRE (TREp) with no basepair gap. T3 enhances the formation and alters the mobility of these complexes on both elements. When positioned up-stream of a heterologous promoter-chloramphenicol acetyltransferase reporter, the TK-TRE conferred T3 regulation by endogenous T3R in GH4C1 cells and by cotransfected chicken T3R alpha 1 in HeLa cells. The TK-TRE does not bind and is not activated by retinoic acid receptor. T3Rs and nuclear proteins from GH4C1, HeLa, and COS1 cells form heterodimers on the TK-TRE which differ in abundance and mobility from heterodimers formed on the TREp. The identification of a TRE in the TK promoter raises the possibility that T3R or related proteins may play important roles in regulating the life cycle of herpes simplex virus.

To evaluate the surgical outcome in, and satisfaction with treatment of, patients undergoing epididymectomy for postvasectomy pain syndrome.A total of 49 patients were included. All participants had undergone epididymectomy for chronic epididymal pain from January 2000 to June 2009. Of the 49 patients, 4 had undergone bilateral epididymectomy, and the total number of procedures was 53: 18 in patients with postvasectomy pain syndrome (group 1, n = 16), 21 in patients with chronic epididymitis and no history of vasectomy (group 2, n = 19), and 14 in patients with an epididymal cyst and no history of vasectomy (group 3, n = 14). The preoperative and postoperative pain scale scores and surgical outcome were analyzed.For the total patient sample, the mean age was 52.91 ± 13.51 years, and the mean body mass index was 24.10 ± 3.22 kg/m(2). The mean duration of pain was 1.3 years (range 0.25-20), and the mean duration of postoperative follow-up was 4.2 years (range 0.05-10.25). The mean preoperative pain score was 6.91 ± 0.97. The mean postoperative pain scale score was 1.92 ± 1.54 (P.01). Statistically significant differences in the preoperative and postoperative pain scores were found for each group: group 1, 5.38 ± 1.47 (range 3-8); group 2, 4.10 ± 1.41 (range 2-6), and group 3, 5.21 ± 1.88 (range 2-8; P = .004). In group 1, excellent surgical outcomes and high patient satisfaction were reported for 94.5% (17 of 18) of the procedures performed.The results of our study have shown that epididymectomy is more effective in patients with a history of vasectomy than in those without.

Fabry disease is a lysosomal storage disease caused by a deficiency of alpha-galactosidase A, which results in aberrant glycosphingolipid metabolism and accumulation of globotriaosylceramide (Gb3). Since a correlation between the level of Gb3 and clinical manifestations of Fabry disease has not been observed, we investigated potential diagnostic biomarkers. Hepatic and renal gene expression of male alpha-galactosidase A-deficient mice (Fabry mice) was compared with that of wild-type mice. Microarray analyses were performed using samples taken before and after intravenous infusion of alpha-galactosidase A. The identified genes were validated using quantitative real-time PCR and Western blot assay. Expression of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8 and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin 2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels after enzyme replacement therapy, although the plasma concentrations of these proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and renal involvement in Fabry disease. Furthermore, these genes are promising targets for developing biomarkers for monitoring disease progression and therapeutic efficacy in patients with Fabry disease.

Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-beta antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-beta antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic CD8(+) T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-beta on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.