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Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.

Background The mechanism through which high‐density lipoprotein (HDL) induces cardioprotection is not completely understood. We evaluated the correlation between cholesterol efflux capacity (CEC), a functional parameter of HDL, and coronary collateral circulation (CCC). We additionally investigated whether A1BP (apoA1‐binding protein) concentration correlates with CEC and CCC. Methods and Results In this case‐control study, clinical and angiographic data were collected from 226 patients (mean age, 58 years; male, 72%) with chronic total coronary occlusion. CEC was assessed using a radioisotope and J774 cells, and human A1BP concentration was measured using enzyme‐linked immunosorbent assay. Differences between the good and poor CCC groups were compared, and associations between CEC, A1BP, and other variables were evaluated. Predictors of CCC were identified by multivariable logistic regression analysis. The CEC was higher in the good than in the poor CCC group (22.0±4.6% versus 20.2±4.7%; P =0.009). In multivariable analyses including age, sex, HDL‐cholesterol levels, age (odds ratio [OR], 0.96; P =0.003), and CEC (OR, 1.10; P =0.004) were identified as the independent predictors of good CCC. These relationships remained significant after additional adjustment for diabetes mellitus, acute coronary syndrome, and Gensini score. The A1BP levels were not significantly correlated with CCC (300 pg/mL and 283 pg/mL in the good CCC and poor CCC groups, respectively, P =0.25) or CEC. Conclusions The relationship between higher CEC and good CCC indicates that well‐functioning HDL may contribute to CCC and may be cardioprotective; this suggests that a specific function of HDL can have biological and clinical consequences.

IntroductionCardiovascular disease (CVD) in patients with diabetes is the leading cause of death. Finding early biomarkers for detecting asymptomatic patients with CVD can improve survival. Recently, plasma proteomics—targeted selected reaction monitoring/multiple reaction monitoring analyses (MRM)—has emerged as highly specific and sensitive tools compared with classic ELISA methods. The objective was to identify differentially regulated proteins according to the severity of the coronary artery atherosclerosis.Research design and methodsA discovery cohort, a verification cohort and a validation cohort consisted of 18, 53, and 228 subjects, respectively. The grade of coronary artery stenosis was defined as a percentage of luminal stenosis of the major coronary arteries. Participants were divided into six groups, depending on the presence of diabetes and the grade of coronary artery stenosis. Two mass spectrometric approaches were employed: (1) conventional shotgun liquid chromatography tandem mass spectrometry for a discovery and (2) quantitative MRM for verification and validation. An analysis of the covariance was used to examine the biomarkers’ predictivity beyond conventional cardiovascular risks.ResultsA total of 1349 different proteins were identified from a discovery cohort. We selected 52 proteins based on the tandem mass tag quantitative analysis then summarized as follows: chemokine (C-X-C motif) ligand 7 (CXCL7), apolipoprotein C-II (APOC2), human lipopolysaccharide-binding protein (LBP) and dedicator of cytokinesis 2 (DOCK2) in diabetes; CXCL7, APOC2, LBP, complement 4A (C4A), vitamin D-binding protein (VTDB) and laminin β1 subunit in non-diabetes. Analysis of covariance showed that APOC2, DOCK2, CXCL7 and VTDB were upregulated and C4A was downregulated in patients with diabetes showing severe coronary artery stenosis. LBP and VTDB were downregulated in patients without diabetes, showing severe coronary artery stenosis.ConclusionWe identified significant associations between circulating APOC2, C4A, CXCL7, DOCK2, LBP and VTDB levels and the degree of coronary artery stenosis using the MRM technique.

Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.

Objectives: The purpose of the study is to investigate the awareness and activation towards dental medical tourism. Methods: A self-reported questionnaire was completed by 195 dental hygienists in Seoul from January 30 to September 15, 2014. Data were analyzed by one way ANOVA, chi square and t test using SPSS 19.0 program. the questionnaire consisted of general characteristics of the subjects, awareness towards medical tourism, medical tourism related hospitals, activation of Korean medical tourism, fields of medical tourism, and improvement of medical tourism. The questionnaire was adapted and modified from Kim and Kim by Likert scale. Results: Dental hygienists gave the high perception and possibility towards medical tourism (94.1%). Those carrying out medical tourism accounted for 39.5 percent. The most difficult problem was communication with foreigners (80.5%). The performance of prosthesis and anesthesia was the most specialized area that supported the medical tourism (84.1%). In order to improve the medical tourism implementation, dental medical technology must be strengthened (39.8%). Conclusion: The desirable dental medical tourism must be carried out by proficient dental medical manpower, higher technology, active participation and financial support by the government. This dental medical tourism will provide job opening for the dental hygienists.

Objective To investigate the patterns and mechanisms of audiovestibular impairments associated with intracranial hypotension. Methods We had consecutively recruited 16 patients with intracranial hypotension at the Neurology Center of Pusan National University Hospital for two years. Spontaneous, gaze-evoked, and positional nystagmus were recorded using 3D video-oculography in all patients, and the majority of them also had pure tone audiometry and bithermal caloric tests. Results Of the 16 patients, five (31.3%) reported neuro-otological symptoms along with the orthostatic headache while laboratory evaluation demonstrated audiovestibular impairments in ten (62.5%). Oculographic analyses documented spontaneous and/or positional nystagmus in six patients (37.5%) including weak spontaneous vertical nystagmus with positional modulation (n = 4) and pure positional nystagmus (n = 2). One patient presented with recurrent spontaneous vertigo and tinnitus mimicking Meniere's disease, and showed unidirectional horizontal and torsional nystagmus with normal head impulse tests during the attacks. Bithermal caloric tests were normal in all nine patients tested. Audiometry showed unilateral (n = 6) or bilateral (n = 1) sensorineural hearing loss in seven (53.8%) of the 13 patients tested. Conclusions Intracranial hypotension frequently induces audiovestibular impairments. In addition to endolymphatic hydrops and irritation of the vestibulocochlear nerve, compression or traction of the brainstem or cerebellum due to loss of CSF buoyancy may be considered as a mechanism of frequent spontaneous or positional vertical nystagmus in patients with intracranial hypotension.

Episodic ataxia type 2 (EA2) is characterized by recurrent attacks of vertigo and ataxia lasting hours triggered by emotional stress or exercise. Although interictal horizontal gaze-evoked nystagmus and rebound nystagmus are commonly observed in patients with EA2, the nystagmus has been rarely reported during the vertigo attack. To better describe exercise-induced nystagmus in EA2, four affected members from three generations of a Korean family with EA2 received full neurological and neuro-otological evaluations. Vertigo was provoked in the proband with running for 10 min to record eye movements during the vertigo attack. We performed a polymerase chain reaction-based direct sequence analysis of all coding regions of CACNA1A in all participants. The four affected members had a history of exertional vertigo, imbalance, childhood epilepsy, headache, and paresthesia. The provocation induced severe vertigo and imbalance lasting several hours, and oculography documented pure downbeat nystagmus during the attack. Genetic analyses identified a nonsense mutation in exon 23 which has been registered in dbSNP as a pathogenic allele (c.3832C>T, p.R1278X) in all the affected members. Ictal downbeat nystagmus in the studied family indicates cerebellar dysfunction during the vertigo attack in EA2. In patients with episodic vertigo and ataxia, the observation of exercise-induced nystagmus would provide a clue for EA2.

We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Microwave irradiation and immersion in solutions have been recommended for denture disinfection. However, the effect of dry conditions and impression materials has not been completely evaluated.The purpose of this study was to evaluate the effectiveness of microwave irradiation and hydrogen peroxide for the disinfection of dental impression materials.Specimens (diameter 10 mm, thickness 2 mm) were made with polyvinyl siloxane. Experimental groups were treated with hydrogen peroxide (group H), microwave irradiation (group M), and a combination of both hydrogen peroxide and microwave irradiation (group MH) for 1 minute, 2 minutes, and 3 minutes. The control group was untreated. The total sample size was 120. The specimens were divided into 2 groups, those exposed to Streptococcus mutans and those exposed to Escherichia coli. The disinfection effect and physical properties (contact angle, compatibility with gypsum, strain in compression, tear strength) were evaluated.All 3 groups (H, M, MH) were effective in reducing the number of colony forming units (CFU) per unit volume (mL) for both S mutans and E coli compared with the control. The most significant reduction in the CFU/mL of both bacteria was noted in the MH group and was used to compare either treatment alone (P.05). No statistically significant difference was noted between the control and treatment groups in terms of all of the physical properties tested (P.05).Microwave irradiation was identified as a useful disinfection method against S mutans and E coli, especially when combined with H2O2, without adversely affecting the physical properties of dental impression materials.

Dizziness/vertigo is a common symptom of posterior circulation stroke and usually accompanies other neurologic symptoms and signs. Although strokes involving the brainstem or cerebellum may produce isolated vestibular syndrome (isolated vertigo or imbalance), the overall frequency and involved structures of isolated vestibular syndrome in the posterior circulation stroke remain uncertain. Isolated vestibular syndrome occurs in approximately 25% of the patients with posterior circulation stroke, and mostly involves the cerebellum, inferior or superior cerebellar peduncles, and caudal lateral or rostral dorsolateral medulla. The occasional negative neuroimaging in patients with acute isolated vascular vertigo highlights the importance of appropriate bedside evaluation in acute vestibular syndrome.

Background and purpose The inferior cerebellar peduncle (ICP) contains various fibres to and from the cerebellum relating to the integration of the proprioceptive and vestibular functions. However, the full clinical features of isolated unilateral ICP lesions have not been defined in humans. Methods Eight consecutive patients with isolated unilateral ICP lesions at the pontine level (six with stroke, one with multiple sclerosis and one with brainstem encephalitis) received bedside neurological and neuro-otological evaluations and underwent laboratory tests including measurements of the subjective visual vertical (SVV) and ocular torsion, bithermal caloric tests and pure tone audiometry. Results All patients developed isolated acute vestibular syndrome (AVS) with ipsilesional spontaneous nystagmus (n = 7) and contralesional ocular tilt reaction (OTR) and/or SVV tilt (n = 7). In view of the normal head impulse test in all patients and skew deviation in one, our patients met the criteria for AVS from central lesions. Five patients showed a directional dissociation between the OTR/SVV tilt and body lateropulsion that fell to the lesion side whilst the OTR/SVVtilt was contraversive. Conclusions A unilateral ICP lesion at the pontine level leads to the development of isolated AVS. However, a negative head impulse test and directional dissociation between OTR/SVV tilt and body lateropulsion may distinguish lesions involving unilateral ICP at the pontine level from those affecting other vestibular structures.

Background and purpose Generalized cerebral ischaemia from cardiovascular dysfunction usually leads to presyncopal dizziness, but several studies reported a higher frequency of rotatory vertigo in cardiovascular patients. Whether generalized cerebral ischaemia due to cardiovascular disorders may produce objective vestibular dysfunction was investigated. Methods Thirty-three patients with orthostatic dizziness/vertigo due to profound orthostatic hypotension and 30 controls were recruited. All participants underwent recording of eye movements during two orthostatic challenging tests: the Schellong and the squatting−standing tests. Most patients had neuroimaging, and patients with abnormal eye movements were subjected to follow-up evaluations. Results Symptoms associated with orthostatic dizziness/vertigo included blurred vision, fainting and tinnitus. Ten (30%) of 33 patients developed rotatory vertigo and nystagmus during the Schellong (n = 5) or squatting−standing test (n = 5). Four of them showed pure downbeat nystagmus whilst five had downbeat and horizontal nystagmus with or without torsional component. Patients with orthostatic nystagmus had shorter duration of orthostatic intolerance than those without nystagmus (1.0 ± 1.6 vs. 11.0 ± 9.7 months, P

Background Surgical scars are crucial cosmetic problem, especially when in exposed areas such as the anterior neck following thyroidectomy. Objective To evaluate the impact of post-thyroidectomy scars on quality of life (QoL) of thyroid cancer patients and identify the relationship between scar characteristics and QoL. Methods Patients with post-thyroidectomy scars on the neck were recruited. QoL was measured using the Dermatology Life Quality Index (DLQI). Scar characteristics were graded according to Vancouver scar scale (VSS) score. Results Ninety-seven patients completed a battery of questions at the time of enrollment. Post-thyroidectomy scars were classified according to morphology as linear flat scars, linear bulging scars, hypertrophic scars or adhesive scars. There were 32 patients (33.0%), 9 patients (9.3%), 41 patients (42.3%) and 15 patients (15.5%), respectively, in each group. The mean total DLQI score was 9.02. Domain 2 (daily activities, 2.87 points), which includes questions about clothing, was the most greatly impacted among patients. The total DLQI scores of patients who have experienced scar-related symptoms were significantly higher than those of patients without symptoms (p

We investigated the current injection, transport, and luminous efficiency behavior of organic light emitting diode (OLED) containing the 5-10 nm-sized gold particles mixed in the polyfluorene-type copolymer. This nanoparticle-conjugated polymer mixture layer was used as hole injection, transport, and light emitting layer for various structures of OLED based on the phosphorescent and fluorescent emitters. Due to the hole trapping at the nanopaticle, carrier injection is significantly reduced while the hole transport behavior is found to be barely affected. Hole trapping of nanoparticle in light emitting layer (at 4.7 approximately 9.4 x 10(-5) w/w fraction) resulted in an enhancement of efficiency (from 5.23 cd/A to 6.50 cd/A). The existence of the outcoupling effect also supports the carrier trapping behavior, which is amended mechanism of the improved efficiency compared to previously reported mechanism of enhanced photoluminescent stability by a hindrance of photo-oxidation.

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disease mediated by autoantibodies and immune complexes. In SLE, a splenectomy to control the thrombocytopenia does not increase the total risk of thrombosis, but tends to increase arterial events. We experienced a patient with lupusanticoagulant positive SLE who developed a venous thrombosis after a splenectomy for the control of thrombocytopenia, which was a very rare case.

Systemic sclerosis is an autoimmune disease characterized by progressive fibrosis of the skin and visceral organs. Myasthenia gravis is also an autoimmune disease characterized by weakness and fatigue of skeletal muscles. The symptoms of systemic sclerosis and myasthenia gravis overlap clinically, so the recognition of disease co-occurrence may be delayed. Co-occurrence of myasthenia gravis and systemic sclerosis is very uncommon and usually diagnosed after use of D-penicillamine for treating the systemic sclerosis. We report a case of a 49-year-old female patient who complained of general weakness and was diagnosed with myasthenia gravis. Four months earlier she was diagnosed with systemic sclerosis with Sjogren’s syndrome and her medications did not include D-penicillamine.

Background: A novel 2009 influenza A (H1N1) virus emerged and disseminated to all over the world. There are few reports on the clinical characteristics of patients with complications. We describe the clinical features of pneumonia in adult patients hospitalized, who have novel influenza infection. Methods: There were 43 adult patients enrolled into the study with pneumonia of 528 hospitalized patients confirmed influenza A (H1N1) virus infection by real-time reverse transcriptase polymerase chain reaction testing, between 24 August 2009 and 31 January 2010. The clinical data of patients with pneumonia were collected retrospectively. Results: There were 22 of 43 (51.2%) influenza patients with pneumonia that had higher risk factors for complications. Compared to 28 patients with influenza A (H1N1) viral pneumonia and 15 patients, who had isolated bacteria from cultures, those with mixed viral and bacterial pneumonia were significantly more likely to have unilobar consolidations on chest radiographs (53.3 vs. 10.7%, p ＜0.01) and higher scores of pneumonia severity index (PSI; 90 [66∼100] vs. 53 [28∼90], p=0.04). Six patients required mechanical ventilation support in an Intensive Care Unit and were more likely to have dyspnea (83.3 vs. 29.3%, p=0.02) and low levels of PaO2 (48.3 [37.0∼70.5] vs 64.0 [60.0∼74.5] mm Hg, p=0.02) and high levels of pneumonia severity index (PSI) score (108.0 [74.5∼142.8] vs. 56.0 [40.5∼91.0], p=0.03). Conclusion: The majority of pneumonia patients infected with novel influenza improved. Chest radiographic findings of unilobar consolidations suggest that mixed pneumonia is more likely. Initial dyspnea, hypoxemia, and high levels of PSI score are associated with undergoing mechanical ventilation support.

Fibrosing mediastinitis is a rare disease that is characterized by the proliferation of dense fibrous tissue of the mediastinum. The pathogenesis of fibrosing mediastinitis is unknown in most cases. However, histoplasmosis, tuberculosis, autoimmune disease, radiation therapy, and other idiopathic fibroinflammatory diseases have been implicated in some cases. Most clinical features are related to an obstruction or compression of the mediastinal structure. Fibrosing mediastinitis is often progressive and occurs diffusely throughout the mediastinum. We encountered a case of fibrosing mediastinitis of a very focal lesion without evidence of mediastinal involvement. The condition was confirmed by biopsy and graft bypass surgery was performed because of SVC syndrome.

Systemic lupus erythematosus (SLE) is a multisystem ic inflammatory disorder mediated by autoantibodies and immune complexes that manifests with a variety of symptoms. Lupus enteritis is a serious complication of SLE and carries a high mortality rate, however the diagnosis is not easy for there are no specific clinical manifestations and laboratory findings. Lupus enteritis usually involves the mesenteric arteries causing ischemic changes of the small and large bowels, and yet rarely involves the rectum. Here, we report a case of a 26-year-old female lupus enteritis patient who presented with atypical abdominal pain. Early diagnosis was made by abdominal pelvic computed tomography (CT) scan, which showed extensive involvement of lupus enteritis from proximal small bowel to rectum. She recovered after being treated with high dose steroid therapy.