Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier

Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.     

Quantitative RT-PCR assay of HER2 mRNA expression in formalin-fixed and paraffin-embedded breast cancer tissues

Detection of human epidermal growth factor receptor 2 gene (HER2, also known as erbB2) expression is a preparatory process to decide a treatment strategy for breast cancer patients. 20-30% of breast cancer patients have HER2 overexpression, and they usually show poor recovery rate. For detection of HER2 expression, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods are conventionally used. Although these methods are accurate and reliable, their time-consuming process and high cost need a concise method with high sensitivity and accuracy. As a complementary method to the current IHC/FISH standard techniques, PCR-based methods have been developed. Here we employed a quantitative PCR method to detect HER2 expression in one hundred ninety nine formalin-fixed and paraffin-embedded (FFPE) breast cancer tissue samples from the patients treated over two years at the Yonsei University Severance Hospital, Republic of Korea. Relative expression of HER2 mRNA in the FFPE samples was analyzed using a quantitative RT-PCR (RT-qPCR) method and the obtained HER2 expression levels were compared with those from IHC/FISH methods. Our results show that the RT-qPCR method was highly concordant with IHC/FISH methods for detecting HER2 expression. Overall sensitivity and specificity of the BrightGen HER2 RT-qDx assay kit (Syantra, Calgary, Canada), which is a kit we used for RT-qPCR analyses, were 93.0% and 89.8% (P < 0.0001), respectively. The diagnostic cut-off value of HER2 RT-qDx for the clinical samples was determined by likelihood ratio, among which the highest likelihood ratio of relative HER2 mRNA levels was over 105.5 (AUC = 0.9466) with the highest sensitivity and specificity. Our study indicates that quantification of HER2 mRNA expression with the RT-qPCR could be an alternative method of conventional IHC/FISH methods.     

Influence of Chronic Sinusitis and Nasal Polyp on the Lower Airway of Subjects Without Lower Airway Diseases

Purpose

Upper and lower respiratory tract pathologies are believed to be interrelated; however, the impact of upper airway inflammation on lung function in subjects without lung disease has not been evaluated. This study investigated the association of CT finding suggesting chronic sinusitis and lung function in healthy subjects without lung disease.

Methods

This was a retrospective study of prospectively collected data from 284 subjects who underwent a pulmonary function test, bronchial provocation test, rhinoscopy, and osteomeatal unit computed tomography offered as a private health check-up option.

Results

CT findings showed that the sinusitis group had a significantly lower FEV1/FVC ratio than subjects without sinusitis finding (78.62% vs 84.19%, P=0.019). Among the sinusitis group, subjects classified by CT findings as the extensive disease group had a slightly lower FEV1/FVC than those of the limited disease group (76.6% vs 79.5%, P=0.014) and the associations were independent of the presence of airway hyperresponsiveness. The subjects with nasal polyp had also lower FEV1 and FEV1/FVC than subjects without nasal polyp (FEV1: 100.0% vs 103.6%, P=0.045, FEV1/FVC: 77.4% vs 80.0%, P=0.005).

Conclusions

CT findings suggesting chronic sinusitis and nasal polyp were associated with subclinical lower airway flow limitation even in the absence of underlying lung disease.     

The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

Purpose

Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA.

Methods

Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis.

Results

MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age).

Conclusions

Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.     

Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal

Background/Aims

A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.

Methods

The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.

Results

Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.

Conclusions

Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.     

A case of obstructive jaundice caused by tuberculous lymphadenitis: A literature review

Obstructive jaundice caused by tuberculous lymphadenitis is a rare manifestation of tuberculosis (TB), with 15 cases having been reported in Korea. We experienced a case of obstructive jaundice caused by pericholedochal tuberculous lymphadenitis in a 30-year-old man. The patient''s initial serum total bilirubin level was 21.1 mg/dL. Abdominal computed tomography revealed narrowing of the bile duct by a conglomerated soft-tissue mass involving the main portal vein. Abrupt obstruction of the common bile duct was observed on cholangiography. Pathologic analysis of a ultrasonography-guided biopsy sample revealed chronic granulomatous inflammation, and an endoscopic examination revealed esophageal varices and active duodenal ulceration, the pathology of which was chronic noncaseating granulomatous inflammation. Hepaticojejunostomy was performed and pathologic analysis of the conglomerated soft-tissue mass revealed chronic granulomatous inflammation with caseation of the lymph nodes. Tuberculous lymphadenitis should be considered in patients presenting with obstructive jaundice in an endemic area.     

Oral health behaviors and metabolic syndrome: the 2008–2010 Korean National Health and Nutrition Examination Survey

Objectives

This study examined whether oral health behaviors are associated with metabolic syndrome (MetS) in Korean adults involved in the 2008–2010 Korea National Health and Nutrition Examination Survey (KNHANES).

Materials and methods

A total of 18,742 subjects (8,034 men and 10,708 women) were included. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement for Asians. Oral health behavior was assessed using a questionnaire included in the KNHANES.

Results

Subjects with MetS brushed their teeth less frequently and used fewer secondary oral products than subjects without MetS (p?<?0.01). As frequency of toothbrushing and number of secondary oral products increased, body mass index, waist circumference, diastolic blood pressure, fasting plasma glucose, triglyceride, and white blood cell count decreased, but high-density lipoprotein–cholesterol increased (all p for trend <0.01). In the multivariable logistic regression models, as frequency of toothbrushing increased, the odds ratios (ORs) for MetS, abdominal obesity, and hyperglycemia are more than one after adjusting for age, gender, education, income, alcohol and tobacco use, physical activity, and the components of MetS. The ORs for MetS, abdominal obesity, and high blood pressure were more than one in subjects who do not use dental floss after adjusting for all covariates.

Conclusion

MetS is associated with infrequent daily toothbrushing and disuse of dental floss in South Korean.

Clinical relevance

Dentists may recommend evaluation for MetS in the patients with infrequent daily toothbrushing and disuse of dental floss.