Providing essential clinical care for non-COVID-19 patients in a Seoul metropolitan acute care hospital amidst ongoing treatment of COVID-19 patients.

We assessed infection control efforts by comparing data collected over 20 weeks during a pandemic under a dual-track healthcare system. A decline in non-COVID-19 patients visiting the emergency department by 37.6% (P<0.01) was observed since admitting COVID-19 cases. However, patients with acute myocardial infarction (AMI), stroke, severe trauma and acute appendicitis presenting for emergency care did not decrease. Door-to-balloon time (34.3 (± 11.3) min vs 22.7 (± 8.3) min) for AMI improved significantly (P<0.01) while door-to-needle time (55.7 (± 23.9) min vs 54.0 (± 18.0) min) in stroke management remained steady (P=0.80). Simultaneously, time-sensitive care involving other clinical services, including patients requiring chemotherapy, radiation therapy and haemodialysis did not change.

Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. METHODS: A literature search through to May 2017 was carried out of PubMed, Embase and the Cochrane Central Register of Controlled Trials. Studies were eligible if they were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i (SGLT2i/DPP4i) against DPP4i±placebo or SGLT2i±placebo and published in English. The primary outcome was change in HbA1c from baseline. RESULTS: Eight RCTs comparing SGLT2i/DPP4i and DPP4i, and five RCTs comparing SGLT2i/DPP4i and SGLT2i, with three RCTs involving both comparisons, were included in the present review. SGLT2i/DPP4i resulted in a greater mean HbA1c reduction [weighted mean difference (WMD]): -0.62%] than did DPP4i alone, which was a much less marked reduction (WMD: -0.35%) than with SGLT2i alone. Also, significant differences in body weight loss from baseline were observed only with SGLT2i/DPP4i vs. DPP4i, but not vs. SGLT2i. The risk of hypoglycaemic events was low and similar between treatment groups. When subjects were stratified based on baseline HbA1c, any reduction by SGLT2i/DPP4i in relation to DPP4i was proportional to baseline HbA1c levels. However, compared with SGLT2i, HbA1c reductions with SGLT2i/DPP4i were modest regardless of baseline HbA1c. CONCLUSION: Combination therapy with SGLT2i and DPP4i is both efficacious and safe. In particular, a marked additional glucose-lowering effect is evident when SGLT2i is combined with or added to DPP4i, and not vice versa. However, baseline HbA1c determined the additional glucose-lowering effects of SGLT2i in combined treatment with DPP4i.

[Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P<0.05). However, it showed no relationship with sex, smoking, hemoptysis, chest pain, dyspnea, histological type, clinical stage, and administration of chemotherapy (P>0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

Molecular identification and phylogenetic analysis of important medicinal plant species in genus Paeonia based on rDNA-ITS, matK, and rbcL DNA barcode sequences.

This study was performed to identify and analyze the phylogenetic relationship among four herbaceous species of the genus Paeonia, P. lactiflora, P. japonica, P. veitchii, and P. suffruticosa, using DNA barcodes. These four species, which are commonly used in traditional medicine as Paeoniae Radix and Moutan Radicis Cortex, are pharmaceutically defined in different ways in the national pharmacopoeias in Korea, Japan, and China. To authenticate the different species used in these medicines, we evaluated rDNA-internal transcribed spacers (ITS), matK and rbcL regions, which provide information capable of effectively distinguishing each species from one another. Seventeen samples were collected from different geographic regions in Korea and China, and DNA barcode regions were amplified using universal primers. Comparative analyses of these DNA barcode sequences revealed species-specific nucleotide sequences capable of discriminating the four Paeonia species. Among the entire sequences of three barcodes, marker nucleotides were identified at three positions in P. lactiflora, eleven in P. japonica, five in P. veitchii, and 25 in P. suffruticosa. Phylogenetic analyses also revealed four distinct clusters showing homogeneous clades with high resolution at the species level. The results demonstrate that the analysis of these three DNA barcode sequences is a reliable method for identifying the four Paeonia species and can be used to authenticate Paeoniae Radix and Moutan Radicis Cortex at the species level. Furthermore, based on the assessment of amplicon sizes, inter/intra-specific distances, marker nucleotides, and phylogenetic analysis, rDNA-ITS was the most suitable DNA barcode for identification of these species.

Molecular identification of the traditional herbal medicines, Arisaematis Rhizoma and Pinelliae Tuber, and common adulterants via universal DNA barcode sequences.

Methods to identify Pinelliae Tuber and Arisaematis Rhizoma are required because of frequent reciprocal substitution between these two herbal medicines and the existence of several closely related plant materials. As a result of the morphological similarity of dried tubers, correct discrimination of authentic herbal medicines is difficult by conventional methods. Therefore, we analyzed DNA barcode sequences to identify each herbal medicine and the common adulterants at a species level. To verify the identity of these herbal medicines, we collected five authentic species (Pinellia ternata for Pinelliae Tuber, and Arisaema amurense, A. amurense var. serratum, A. erubescens, and A. heterophyllum for Arisaematis Rhizoma) and six common adulterant plant species. Maturase K (matK) and ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) genes were then amplified using universal primers. In comparative analyses of two DNA barcode sequences, we obtained 45 species-specific nucleotides sufficient to identify each species (except A. erubescens with matK) and 28 marker nucleotides for each species (except P. pedatisecta with rbcL). Sequence differences at corresponding positions of the two combined DNA barcodes provided genetic marker nucleotides that could be used to identify specimens of the correct species among the analyzed medicinal plants. Furthermore, we generated a phylogenetic tree showing nine distinct groups depending on the species. These results can be used to authenticate Pinelliae Tuber and Arisaematis Rhizoma from their adulterants and to identify each species. Thus, comparative analyses of plant DNA barcode sequences identified useful genetic markers for the authentication of Pinelliae Tuber and Arisaematis Rhizoma from several adulterant herbal materials.

Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension.

Persistent excessive sympathetic activation greatly contributes to the pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex with positive feedback characteristics. Humoral factors such as bradykinin, adenosine and reactive oxygen species produced in myocardium due to myocardial ischaemia stimulate cardiac sympathetic afferents and thereby reflexly increase sympathetic activity and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and hypertension. The enhanced CSAR at least partially contributes to the sympathetic activation and pathogenesis of these diseases. Nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla are the most important central sites involved in the modulation and integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase-derived superoxide anions pathway in the PVN are mainly responsible for the enhanced CSAR in CHF and hypertension. Central angiotensin-(1-7), nitric oxide, endothelin, intermedin, hydrogen peroxide and several other signal molecules are involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF and hypertension. This review focuses on the anatomical and physiological basis of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the role of enhanced CSAR in the pathogenesis of CHF and hypertension.

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma.

Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the "pathogenic" A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.

Mitochondrial ND3 G10398A mutation: a biomarker for breast cancer.

Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.

Apelin-13 and APJ in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats.

AIMS: Apelin is a specific endogenous ligand of orphan G protein-coupled receptor APJ. This study was designed to determine the roles and mechanisms of apelin-13 and APJ in paraventricular nucleus (PVN) in renal sympathetic nerve activity (RSNA), arginine vasopressin (AVP) release and mean arterial pressure (MAP) in spontaneously hypertensive rats (SHR). METHOD: Acute experiment was carried out in 13-week-old male SHR and Wistar-Kyoto rats (WKY) under anaesthesia. RSNA and MAP responses to the PVN microinjection were determined. Apelin and APJ expressions were examined with quantitative real-time PCR and Western blot. AVP and noradrenaline were determined with ELISA. Osmotic minipumps were used for chronic PVN infusion in conscious WKY. RESULTS: Apelin and APJ in the PVN were up-regulated in SHR. The PVN microinjection of apelin-13 increased, but APJ antagonist F13A decreased the RSNA, MAP, plasma noradrenaline and AVP levels in SHR. N-methyl-D-aspartate receptor (NMDAR) antagonist plus non-NMDAR antagonist abolished the apelin-13-induced sympathetic activation rather than AVP release. NMDAR antagonist or non-NMDAR antagonist alone attenuated the apelin-13-induced sympathetic activation. Chronic infusion of apelin-13 into the PVN in normotensive rats induced hypertension, increased plasma noradrenaline and AVP levels and promoted myocardial atrial natriuretic peptide and beta-myosin heavy chain mRNA expressions, two indicative markers of cardiac hypertrophy. CONCLUSION: Apelin-13 and APJ in the PVN contribute to hypertension via sympathetic activation and AVP release in SHR. The sympatho-excitatory effect of apeline-13 is mediated by both NMDAR and non-NMDAR in the PVN. Persistent activation of APJ in the PVN induces hypertension.

Serum bilirubin as a predictor of incident metabolic syndrome: a 4-year retrospective longitudinal study of 6205 initially healthy Korean men.

AIM: Serum bilirubin is an endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with oxidative stress-mediated diseases, including the metabolic syndrome (MetS). However, the clinical relevance of bilirubin as a risk factor for incident MetS remains controversial. For this reason, the longitudinal effects of baseline serum bilirubin concentrations on incident MetS were evaluated in Korean men. METHODS: This 4-year retrospective longitudinal observational study involved 6205 Korean men without MetS. Subjects underwent routine health examinations in 2007 and returned for a follow-up examination in 2011. Baseline serum bilirubin concentrations were determined using the vanadate oxidation method. RESULTS: During the 4-year period, 936 cases of incident MetS (15.1%) were identified. Its incidence decreased across baseline bilirubin quartile categories (P<0.001), with an odds ratio (OR) for developing MetS being significantly lower in the highest quartile group (≥ 1.40 mg/dL) compared with the lowest (≤ 0.90 mg/dL) after adjusting for all confounding variables [OR=0.70, 95% confidence interval (CI) 0.54-0.90; P for trend=0.019]. Among individual components of MetS, bilirubin was found to be negatively associated with only the risk of incident hypertriglyceridaemia. The OR (95% CI) for incident hypertriglyceridaemia in the highest vs lowest quartile was 0.75 (0.61-0.91; P for trend=0.002). CONCLUSION: Serum total bilirubin level was negatively associated with incidence of MetS in healthy Korean men over a 4-year period.

Superoxide anions involved in sympathoexcitation and pressor effects of salusin-ß in paraventricular nucleus in hypertensive rats.

AIMS: Salusin-ß in paraventricular nucleus (PVN) increases renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR) and arginine vasopressin (AVP) release in hypertensive rats but not in normal rats. The present study was designed to investigate the downstream molecular mechanism of salusin-ß in the PVN in hypertension. METHOD: Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male SD rats. Acute experiments were carried out 4 weeks after 2K1C or sham operation under anaesthesia. RESULTS: MrgA1 mRNA expression and salusin-ß level in the PVN as well as plasma salusin-ß level were increased in 2K1C rats. Bilateral PVN microinjection of salusin-ß increased the RSNA, MAP and HR in 2K1C rats, which were abolished by the pre-treatment with polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide anion scavenger tempol, the NAD(P)H oxidase inhibitor apocynin or the protein kinase C (PKC) inhibitor chelerythrine chloride (CLC), but not affected by the AT1 receptor antagonist losartan, the Mas receptor antagonist A-779, the NOS inhibitor L-NAME or the GABAA and GABAB receptor antagonists gabazine+CGP-35348. Salusin-ß-induced increases in superoxide anion level and NAD(P)H oxidase activity in the PVN were abolished by the PVN pre-treatment with CLC. Salusin-ß increased AVP levels in rostral ventrolateral medulla and plasma, which were prevented by the pre-treatment with PEG-SOD, apocynin or CLC in 2K1C rats. Salusin-ß augmented the enhanced activity of PKC in the PVN in 2K1C rats. CONCLUSION: Protein kinase C-NAD(P)H oxidase-superoxide anions pathway in the PVN is involved in salusin-ß-induced sympathetic activation, pressor response and AVP release in renovascular hypertension.

Ionotropic glutamate receptors in paraventricular nucleus mediate adipose afferent reflex and regulate sympathetic outflow in rats.

AIM: Chemical stimulation of white adipose tissue (WAT) induces adipose afferent reflex (AAR) and results in increases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). The enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate whether N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR in paraventricular nucleus (PVN) modulate AAR and sympathetic outflow. METHODS: Renal sympathetic nerve activity and MAP were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to the injection of capsaicin into the four sites of right inguinal WAT (8.0 nmol for each site). RESULTS: Bilateral PVN microinjection of NMDAR antagonist AP5 or MK-801, or non-NMDAR antagonist CNQX attenuated AAR, RSNA and MAP. AP5 + CNQX caused greater effects than AP5 or CNQX alone and almost abolished AAR. NMDAR agonist NMDA or non-NMDAR agonist AMPA enhanced the AAR, and increased RSNA and MAP, which were prevented by AP5 or CNQX pre-treatment respectively. Casein kinase 2 inhibitor DRB, NR2A antagonist NVP-AAM077 or NR2B antagonist CP-101,606 attenuated AAR, RSNA and MAP. NVP-AAM077 + CP-101,606 caused greater effects than NVP-AAM077 or CP-101,606 alone. Bilateral baroreceptor denervation and vagotomy enhanced AAR, which was abolished by PVN pre-treatment with AP5 + CNQX. Furthermore, AP5 + CNQX abolished the AAR induced by leptin in iWAT. CONCLUSION: Both NMDAR and non-NMDAR in the PVN mediate AAR and contribute to the tonic control of sympathetic outflow and blood pressure. CK2, NR2A and NR2B subunits of NMDAR in the PVN are involved in the NMDAR-mediated tonic control of AAR, RSNA and MAP.

CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.

Morphological comparison of small nerve fibres in gastric mucosa in non-diabetic and Type 2 diabetic subjects.

AIM: To determine changes in small nerve fibres in gastric mucosa in patients with Type 2 diabetes by morphological observation. METHODS: In twenty-five non-diabetic and 21 Type 2 diabetic participants, gastric mucosal biopsy under endoscopy was performed. Innervation in gastric mucosa was detected using immunohistochemical staining. Anti-protein gene product (PGP) 9.5 positive nerves underwent morphological observation and quantitative analysis. RESULTS: Small nerve fibres in gastric mucosa were shortened in the diabetic subjects. The ratio of gastric mucosal protrusions maintaining nerve fibres between gastric pits to total observed protrusions was lower in patients with Type 2 diabetes compared with the non-diabetic subjects (ratio of innervated protrusion/total protrusion: 0.49 +/- 0.12 vs. 0.89 +/- 0.06, P < 0.05). CONCLUSIONS: This study sets the scene for further research to investigate the relationship between gastric mucosal nerves and autonomic neuropathy or diabetic peripheral neuropathy.

HLA-DRB1*0908, a new allele was identified by sequence-based typing in a Korean individual.

A new human leukocyte antigen DRB1*0908 differs from GTC to AGC in DRB1*090102 at codon 57 with a coding change, valine to serine.

Combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.

OBJECTIVE: To determine the efficacy and safety of the combination of leflunomide and methotrexate for the treatment of patients with active rheumatoid arthritis (RA) in an open, non-comparative, multicentre trial. METHODS: Seventy-four patients with active RA were enrolled to receive concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks. The primary end-point was a 20% improvement in the American College of Rheumatology (ACR) criteria at 20 weeks. Safety measures included evaluation of adverse events at each visit and laboratory data, including haematology and liver function tests. Intention-to-treat analyses were conducted. RESULTS: Sixty-five patients completed 20 weeks of treatment, and 71.6% were responders based on the ACR20 criteria. After 20 weeks, the mean changes were -16.3 for tender joint count, -12.0 for swollen joint count, -44.0 for physician global assessment, -34.3 for patient global assessment, -22.7 for erythrocyte sedimentation rate, and -0.65 for the Health Assessment Questionnaire score. Adverse events occurred in 40.5% of the patients, and were considered serious in four patients who discontinued therapy. Abnormal liver function was noted for 16 patients (21.6%). Two of these patients were withdrawn from the study; after discontinuing the medication, their liver function recovered fully. CONCLUSION: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents.

Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria.

BACKGROUND: Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N-methyltransferase (HNMT). OBJECTIVE: To investigate the functional variability of HNMT gene in relation to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU). METHODS: Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3'-untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'-UTR reporter construct to examine mRNA stability and fluorescence-tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'-UTR construct and in the patients' red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined. RESULTS: The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils. CONCLUSION: The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.

Polymorphisms in the type IV collagen alpha3 gene and the risk of COPD.

A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as the most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesised that the type IV collagen alpha3 (COL4A3) gene, which is one of the genes located in the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of COL4A3 -1162T>C, IVS2+12C>A, P141L, G162E, H451R, P574L and *315C>A polymorphisms with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The presence of at least one 451R allele was associated with a significantly higher risk of COPD compared with the 451 H/H genotype (adjusted odds ratio 1.48, 95% confidence interval (1.03-2.14)). When the subjects were stratified according to age and COPD severity, the 451R allele was associated with a significantly higher risk of COPD only in younger individuals with severe COPD (3.02 (1.37-6.67)). In conclusion, these findings suggest that the type IV collagen alpha3 gene contributes to the genetic susceptibility to chronic obstructive pulmonary disease.

Characteristics of emissions of air pollutants from burning of incense in temples, Hong Kong.

Field investigations of target air pollutants at two of the most famous temples in Hong Kong were conducted. The air pollution problems in these two temples during peak and non-peak periods were characterized. The target air pollutants included particulate matters (PM(10), PM(2.5)), volatile organic compounds (VOCs), carbonyl compounds, carbon monoxide (CO), nitrogen oxides (NO(x)), methane (CH(4)), non-methane hydrocarbons (NMHC), organic carbon (OC), elemental carbon (EC), and inorganic ions (Cl(-), NO(3)(-), SO(4)(2-), Na(+), NH(4)(+), and K(+)). The pollutant levels of the two temples during peak period were shown to be significantly higher than those during non-peak period. The highest average CO level was obtained at Temple 1 during peak period, which exceeded IAQO 8-h Good Class criteria. In general, the average PM(2.5)/PM(10) ratios were approximately 82%. The results revealed that the fine particulates (PM(2.5)) constituted the majority of suspended particulates at both temples. It was noted that formaldehyde was the most abundant carbonyl compounds, followed by acetaldehyde. At Temple 1 during peak period, the average benzene concentration exceeded almost 8 times more than Indoor Air Quality Objectives for Office Buildings and Public Places (IAQO) [HKEPD, 2003. Guidance notes for the management of indoor air quality in offices and public places. Indoor air quality management group, The Government of the Hong Kong Special Administrative Region.] Good Class criteria. The average OC/EC ratios ranged from 2.6 to 17 in PM(10) and from 4.2 to 18 in PM(2.5) at two temples, which suggested that OC measured in these two temple areas may be due to both direct emission from incense burning and secondary formation by chemical reactions. The total mass of inorganic ions, organic carbon, and elemental carbon accounted for about 71% in PM(2.5) and 72% in PM(10).

Glucocorticoid-induced tumour necrosis factor receptor-related protein-mediated macrophage stimulation may induce cellular adhesion and cytokine expression in rheumatoid arthritis.

Glucocorticoid-induced tumour necrosis factor receptor (TNFR)-related protein (GITR) is one of the T cell co-stimulatory molecules and is associated with the pathogenesis of a number of autoimmune diseases. We investigated the expression patterns of GITR in human arthritic synovium and the role of GITR in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemical analyses revealed the expression of GITR and its cognate ligand, GITRL, in macrophages in RA, but not in osteoarthritis (OA), synovium. To investigate the role of GITR in macrophage functions, primary macrophages from RA patients and a human macrophage cell line, THP-1, were analysed. Stimulation of the macrophages with anti-GITR monoclonal antibody induced up-regulation of intercellular adhesion molecule (ICAM)-1 and subsequent aggregation/adhesion, which was enhanced by the presence of extracellular matrix proteins and blocked by anti-ICAM-1 monoclonal antibody. The validity of these in vitro observations was confirmed by immunohistochemical analyses of RA synovium, which showed strong expression of ICAM-1 in GITR-positive macrophages. Additionally, GITR stimulation induced expression of proinflammatory cytokines/chemokines and matrix metalloproteinase-9 in synovial macrophages. These data indicate that GITR, expressed on macrophages in human RA synovium, may enhance inflammatory activation of macrophages by promoting cytokine gene expression and adhesion between cells and to extracellular matrix in RA synovium.