The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300–0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC.
macrophage; non-small cell lung cancer; epidermal growth factor receptor; survival analysis
Acinar cell carcinoma (ACC) is a rare pancreatic tumour with a favourable prognosis compared with the more common ductal adenocarcinoma. The radiological findings of this tumour have been described in the literature; however, only limited data are available regarding the metastatic features of ACC of the liver, the most common metastatic site. We report a case of ACC of the pancreas with a hepatic metastasis from a benign-appearing malignant pancreatic lesion.
To determine the prognostic factors and treatment outcomes of patients with early-stage adenocarcinoma (AdCa) of uterine cervix who underwent radical hysterectomy (RH).
Patients with early-stage squamous cell carcinoma (SCCa) of the uterine cervix who underwent RH were compared with patients with AdCa by multivariate analysis.
A total of 1218 patients were eligible, of which 996 (81.8%) had SCCa and 222 (18.2%) had AdCa. In multivariate analysis, parametrial involvement and lymph node metastasis were significant factors for both recurrence-free survival(RFS) and overall survival (OS) of patients with AdCa, whereas age, tumour size, parametrial involvement and lymph node metastasis were significant factors for both RFS and OS of patients with SCCa. After adjusting for significant prognostic factors, patients with AdCa had significantly poorer RFS (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.37–3.12, P=0.001) and OS (OR=2.56, 95% CI=1.65–3.96, P<0.001) than patients with SCCa. Recurrence outside the pelvis was more frequent in AdCa than in those with SCCa (75 vs 57.8%, P=0.084).
Although RH is still acceptable for treatment of patients with AdCa, a more effective systemic adjuvant therapy is required.
early-stage cervical cancer; squamous cell carcinoma; adenocarcinoma; radical hysterectomy; prognosis
Black rice is rich in anthocyanin and is expected to have more healthful dietary potential than white rice. We assessed expression of anthocyanin in black rice cultivars using a newly designed 135 K Oryza sativa microarray. A total of 12,673 genes exhibited greater than 2.0-fold up- or down-regulation in comparisons between three rice cultivars and three seed developmental stages. The 137 transcription factor genes found to be associated with production of anthocyanin pigment were classified into 10 groups. In addition, 17 unknown and hypothetical genes were identified from comparisons between the rice cultivars. Finally, 15 out of the 17 candidate genes were verified by RT-PCR analysis. Among the genes, nine were up-regulated and six exhibited down-regulation. These genes likely play either a regulatory role in anthocyanin biosynthesis or are related to anthocyanin metabolism during flavonoid biosynthesis. While these genes require further validation, the results here underline the potential use of the new microarray and provide valuable insight into anthocyanin pigment production in rice.
Anthocyanin; Black rice; Pigmentation; Rice microarray; Transcription factor
To understand patients' perceptions of clinical trials (CTs) is the principal step in the enrolment of patients to CTs. However, these perceptions in eastern countries are very rare. From 12 February 2007 to 13 April 2007, we consecutively distributed the questionnaire to 842 cancer patients who initiated a first cycle of chemotherapy regardless of each treatment step in the Seoul National University Hospital. Younger age, higher educational degree, higher economic status, and possession of private cancer insurance were related with significantly higher awareness of CTs (P=0.001, P=0.006, P=0.002, and P=0.009, respectively). However, unlike awareness, perceptions on benefits of CTs were not changed according to age, educational degree, and economic status (P=0.709, P=0.920, and P=0.847, respectively). Willingness was also not changed according to age, educational degree, economic status, and private cancer insurance (P=0.381, P=0.775, P=0.887, and P=0.392, respectively). Instead, males and heavily treated patients had more positive perceptions on benefits (P=0.002 and P=0.001, respectively) and more willingness to participate in CTs (OR=1.17, 1.14–2.75: OR=1.59, 1.01–2.51, respectively). In summary, cancer patients' awareness of CTs, perceptions on the benefit in CTs, and willingness to participate are differently influenced by diverse medical and social conditions. This information would be very helpful for investigators to properly conduct CTs in eastern cancer patients.
cancer patient; clinical trial; perception; awareness; willingness
Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non‐productive chronic cough have not been reported.
Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin‐1 and neurokinin‐2 receptors (NK‐1R and NK‐2R, respectively). Informative non‐synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK‐1R and NK‐2R genotypes was evaluated.
Two informative SNPs were identified in NK‐2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK‐1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)]. Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) μM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) μM/l, p = 0.03).
The results of this study suggest that NK‐2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.
chronic cough; neurokinin receptors; polymorphism; capsaicin sensitivity
Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125–6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.
Citrus red mite (CRM) is known as the most common sensitizing allergen in subjects with asthma and rhinitis working on citrus farms. The aim of this study is to evaluate the role of specific IgG1 (slgG1) and specific IgG4 (slgG4) to CRM in citrus farmers. Questionnaire survey and skin prick test including CRM antigen was done by 136 workers. Specific IgE (slgE), slgG1 and slgG4 to CRM were detected by enzyme-linked immunosorbent assay (ELISA). CRM-sensitive-asthma was diagnosed upon presence of asthmatic symptoms by questionnaire, airway hyperresponsiveness to methacholine and slgE to CRM. CRM-sensitive rhinitis was diagnosed upon presence of rhinitis symptoms and slgE to CRM. Eleven (8.1%) had CRM-sensitive asthma and 25 (18.4%) had CRM-sensitive rhinitis. Significant association was noted between presence of asthmatic symptoms and slgE or slgG4 (p<0.05, respectively), while no significant association was noted in slgG1 (p>0.05). Significant association was noted in the prevalence between slgG4 and slgE (p<0.05), while no significant association was noted between slgG1 and slgG4 or slgE (p<0.05, respectively). There was a significant correlation between slgE and slgG4 level (r=0.39, p<0.05). These findings suggest that the presence of slgG1 to CRM is response to CRM exposure, and further studies will be needed to evaluate the role of slgG4.
To compare the mediator releasability between atopic and nonatopic asthmatics, we measured basophil histamine releasability (BaHR) using a calcium-ionophore A23187 and anti-IgE in 137 subjects who were treated at Seoul National University Hospital. Subjects were categorized into atopic (group AA, n=77) or nonatopic asthmatics (group NA, n=32), or normal controls (group NC, n=28). Serum total IgE levels were determined and correlation with BaHR was assessed. Anti-IgE-induced maximal BaHR in groups AA, NA, and NC was 41.0+/-3.2, 23.1+/-4.5, and 16.8+/-3.8, respectively (mean+/-SE, %). Anti-IgE-induced BaHR in group AA was significantly higher than that in groups NA and NC (p<0.05). Calcium ionophore A23187-induced maximal BaHR was 43.1+/-2.8, 40.8+/-4.4, and 50.5+/-5.2, respectively (mean+/-SE, %), and there was no significant difference among the groups. Serum total IgE level correlated significantly with anti-IgE-induced maximal BaHR (r=0.281, p<0.01) but not with that induced by calcium ionophore A23187. In conclusion, IgE receptor-related BaHR is higher in atopic asthmatics than in nonatopic asthmatics, and this increased BaHR in atopics is significantly associated with increased serum total IgE level.
CD44 is a member of cell surface glycoproteins which are involved in cell-matrix adhesion and tumor metastasis. Certain types of tumors express complex CD44 isoforms generated by alternative splicing of 2v-10v exons, and their expression appears to promote metastasis of tumor cells. Using a nested RT-PCR, we analyzed expression of CD44 variants in 26 stomach carcinoma, 21 matched normal tissues, and 2 carcinoma cell lines. We observed frequent and complex patterns of CD44 variant expression in tumor tissues. While exons 6v and 7v expression was detected in most normal and tumor tissues, exon 9v was most rarely detected. Exon 5v showed a significantly frequent expression in carcinoma, suggesting that its expression might contribute to the malignant progression. While exon 9v was frequently observed in diffuse-type tumors, the other 8 variant exons including 6v showed more frequent expression in intestinal-type tumors. Exons 9v and 10v were predominantly expressed in advanced tumor tissues and exon 8v was expressed more frequently in tumors of lymph node metastasis. We believe that series with a longer follow-up now need to be tested to clarify the association between CD44 splice variant expression and distant metastasis or long-term prognosis.
Insertion of methyl methacrylate polymer into newly reamed bony cavities has sometimes resulted in profound hypotension, cardiac arrest, or sudden death which are more common in patients with hemodynamic instability or hypovolemia. In paralysis agitans(Parkinson's disease), dramatic worsening of the disease often occurs when another illness or trauma accompanies it. And it is possible that chronic medication with levodopa can cause the loss of ability to support blood pressure. So, it involves some risk to use methyl methacrylate in chronic levodopa-treated paralysis agitans. We present a case of paralysis agitans who demonstrated profound hypotension immediately following insertion of methyl methacrylate polymer in spite of normovolemia and proper anesthetic management.
We report five cases of cytomegalovirus infection in immunocompromised patients which were detected by either cytomegalovirus antigenemia assay or in situ hybridization. Four cases had leukemia and the other had chronic renal failure. All the three BMT recipients suffered from GvHD. Interestingly, there was an unique case of CMV disease without a history of BMT, which reminded us that CMV could attack immunocompromised patients who had not undergone transplantation, too. Four out of five cases died. We think that cytomegalovirus infection or disease should not be regarded as a minor problem in post-transplantation infection in Korea.
A case of malacoplakia of the prostatic gland associated with prostatic nodular hyperplasia from a 69 years old man was presented, and its light and electron microscopic and immunohistochemical features were discussed along with its pathogenesis. This lesion was incidentally found in a transurethral prostatectomy specimen, and consisted of large number of epithelioid cells in which were typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. Ultrastructurally, these inclusions showed a dense, central calcified bodies of various developmental stages. Immunohistochemical study using antilysosomal antibody revealed no lysosomal activity. Based on these findings, we could suspect that main problem for this development of malacoplakia is altered intracellular digestion process of foreign biologic materials.
Zymogram studies of peptide hydrolases from the human intestinal brush border and cytoplasmic fractions produced multiple bands--that is, up to seven--while the brush border membrane produced only a single band of enzyme activity. With all of the substrates tested except L-leucyl-L-leucyl-L-leucine, a band having anodic mobility identical with that produced by the brush border enzymes was produced by the cytoplasmic enzymes. With L-trileucine as a substrate, no overlapping band was produced. This band in the cytoplasmic fraction was heat sensitive, while that in the brush border fraction was not. Thus it would appear that there is a single human intestinal brush border peptide hydrolase capable of hydrolysing a variety of di- and tri-peptides. This peptide hydrolases of the brush border and the cytoplasmic fraction of human intestine are distinct.
Peptide hydrolases, catalyzing the hydrolysis of 13 dipeptides and 5 tripeptides into their respective amino acids, were studied in small intestinal mucosa and other tissues, in man and in the rat.
Studies on the subcellular distribution of these enzymes showed enzyme activities in both the soluble and brush border fractions of the rat small intestinal mucosa, the former constituting 80-90% and the latter 10-15% of the total activity. Zymogram studies of peptide hydrolases, in both fractions, yielded multiple bands indicating multiple zones of enzyme activity. With most substrates a rather broad range of enzyme activities was observed in the soluble fraction differing only slightly from substrate to substrate, the exception being when L-leucyl-L-proline was used: this latter led to a zymogram pattern which was quite distinct. The synthetic substrates, L-leucyl-β-naphthylamide and L-leucinamide appeared to be hydrolyzed by two electrophoretically distinct enzymes, different from those hydrolyzing other leucyl-containing peptide substrates.
Zymogram patterns of the brush border membrane fraction were quite different from those of the soluble fraction of rat small intestine indicating that enzymes from the two sources may be different. No comparable human data were obtained.
Peptide hydrolases in the soluble fractions of various organs from the same species gave similar zymogram patterns, while those from the plasma membrane-bound fractions of different organs in the same species were peculiar to each organ. From these data, it is suggested that peptide hydrolases in the brush border and the soluble fractions of small intestine are distinct enzymes and may play different roles in cellular function.
Recently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD.
Extracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects.
The in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects.
These results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.
atopic dermatitis; extracellular vesicles; skin inflammation; Staphylococcus aureus
Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses.
To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens.
Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 μg of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs.
The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins.
These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens.
asthma; airway immune dysfunction; extracellular vesicles; lipopolysaccharide
Cancer research has been devoted toward an understanding of the molecular regulation and functional significance of cell-cycle regulators in the pathogenesis and development of cancers. Cyclin-dependent Kinase 2-associated Protein 1 (CDK2AP1) is one such cell-cycle regulator, originally identified as a growth suppressor and a prognostic marker for human oral/head and neck cancers. Functional importance and the molecular mechanism of CDK2AP1-mediated cell-cycle regulation have been documented over the years. Recent progress has shown that CDK2AP1 is a competency factor in embryonic stem cell differentiation. Deletion of CDK2AP1 leads to early embryonic lethality, potentially through altered differentiation capability of embryonic stem cells. More intriguingly, CDK2AP1 exerts its effect on stem cell maintenance/differentiation through epigenetic regulation. Cancer cells and stem cells share common cellular characteristics, most prominently in maintaining high proliferative potential through an unconventional cell-cycle regulatory mechanism. Cross-talk between cellular processes and molecular signaling pathways is frequent in any biological system. Currently, it remains largely elusive how cell-cycle regulation is mechanistically linked to epigenetic control. Understanding the molecular mechanism underlying CDK2AP1-mediated cell-cycle regulation and epigenetic control will set an example for establishing a novel and effective molecular link between these two important regulatory mechanisms.
Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1); cell cycle; epigenetic regulation; oral/head and neck cancer; embryonic stem cells; cancer stem cells
The objective of this study was to evaluate the usefulness of bone scan procedures for the diagnosis of temporomandibular joint (TMJ) osteoarthritis.
From February 2009 to June 2009, 22 patients (4 males and 18 females) from Seoul National University Bundang Hospital, Republic of Korea, were diagnosed with TMJ disorder. They were examined by clinical examination, plain radiograph and bone scan and were categorized into three groups: normal, internal derangement and osteoarthritis. TMJ uptake ratios and asymmetrical indices were calculated.
There were no significant differences in uptake ratios associated with pain and bone change. However, significant results were obtained when comparing uptake ratios between the osteoarthritis and non-osteoarthritis groups.
It was concluded from this study that bone scans may help to diagnose osteoarthritis when increased uptake ratios are observed.
osteoarthritis; temporomandibular joint; bone scan
CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.
Methods and results:
The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.
CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.
CD151; breast cancer; five subtypes; prognosis; tetraspanin
We compared vertebral fracture assessment by semi-automated quantitative vertebral morphometry measurements with the conventional semi-quantitative (SQ) grading using lateral CT scout views. The semi-automated morphometry method showed good to excellent agreement with the visual SQ grading by radiologists for identification of vertebral fractures.
Semi-automated quantitative vertebral morphometry (QM) measurements may enhance management of osteoporosis patients by providing an efficient means to identify vertebral fractures (VFx). We compared identification of prevalent VFx by semi-automated QM to SQ grading.
A non-radiologist performed semi-automated QM from CT lateral scout views in 200 subjects (102 men, 98 women, 65.8±8.9 years) selected from the Framingham Heart Study Multidetector CT Study. VFx were classified in the QM approach based on using Genant’s criteria for deformities, and compared with conventional SQ grading performed by experienced radiologists as the gold standard. The kappa (k) statistics, percent agreement (% Agree), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were computed.
Among 200 subjects, 57 had mild and 41 had moderate or severe VFx by visual SQ grading. Per-person analyses showed excellent agreement between the two methods, with k=0.780. The % Agree ranged from 86.7% to 91.2%, the SE was 81.3%–96%, and the SP was 86.5%–92%. Among 2,588 vertebrae analyzed, 107 had mild and 49 had moderate or severe VFx by visual SQ grading. Per-vertebra analyses revealed good agreement, with k=0.580. Agreement between the methods tended to be highest in L1-L4 region. Agreement and validity measures were higher when only moderate and severe fractures were included.
The semi-automated quantitative vertebral morphometry measurements from CT lateral scout views provided good to excellent agreement with the standard SQ grading for assessment of prevalent vertebral fractures.
Computed tomography; Quantitative vertebral morphometry; Semi-automated vertebral morphometry; Semi-quantitative; Validity; Vertebral fracture
To determine the prevalence and incidence of epilepsy among US Medicare beneficiaries aged 65 years old and over, and to compare rates across demographic groups.
We performed a retrospective analysis of Medicare administrative claims for 2001–2005, defining prevalent cases as persons with ≥1 claim with diagnosis code 345.xx (epilepsy) or 2 or more with diagnosis code 780.3x (convulsion) ≥1 month apart, and incident cases as prevalent cases with 2 years immediately before diagnosis without such claims. Prevalence and incidence rates were calculated for the years 2003–2005 using denominators estimated from a 5% random sample of Medicare beneficiaries. Results were correlated with gender, age, and race.
We identified 282,661 per year on average during 2001–2005 (a total of 704,243 unique cases overall), and 62,182 incident cases per year on average during 2003–2005. Average annual prevalence and incidence rates were 10.8/1,000 and 2.4/1,000. Overall, rates were higher for black beneficiaries (prevalence 18.7/1,000, incidence 4.1/1,000), and lower for Asians (5.5/1,000, 1.6/1,000) and Native Americans (7.7/1,000, 1.1/1,000) than for white beneficiaries (10.2/1,000, 2.3/1,000). Incidence rates were slightly higher for women than for men, and increased with age for all gender and race groups.
Epilepsy is a significant public health problem among Medicare beneficiaries. Efforts are necessary to target groups at higher risk, such as minorities or the very old, and to provide the care necessary to reduce the negative effects of epilepsy on quality of life.
Currently, serum biomarkers, which are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinoma do not exist. Therefore, this study identified a panel of serum biomarkers for the diagnosis of gastric adenocarcinoma.
A 29-plex array platform with 29 biomarkers, consisting of 11 proteins discovered through proteomics and 18 previously known to be cancer-associated, was constructed. A test/training set consisting of 120 gastric adenocarcinoma and 120 control samples were examined. After 13 proteins were selected as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 95 gastric adenocarcinoma and 51 control samples.
Epidermal growth factor receptor (EGFR), pro-apolipoprotein A1 (proApoA1), apolipoprotein A1, transthyretin (TTR), regulated upon activation, normally T-expressed and presumably secreted (RANTES), D-dimer, vitronectin (VN), interleukin-6, α-2 macroglobulin, C-reactive protein and plasminogen activator inhibitor-1 were selected as classifiers in the two algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (>88%). These algorithms also accurately classified in the validation set (>85%).
Two panels of combinatorial biomarkers, including EGFR, TTR, RANTES, and VN, are developed, which are less invasive method for the diagnosis of gastric adenocarcinoma. They could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy.
biomarker; gastric adenocarcinoma; diagnosis; screening
Noroviruses are a common cause of gastrointestinal disease in humans worldwide. Here, we report the full-length genomic characterization of GII.4 norovirus strain HS191, which was associated with gastroenteritis in a laboratory worker in 2004.