The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

Rheumatoid arthritis (RA) is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF). The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insufficient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specific antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specificity (98%) for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody), can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA

Mitral valve prolapse associated with celiac artery stenosis: a new ultrasonographic syndrome?

BACKGROUND: Celiac artery stenosis (CAS) may be caused by atherosclerotic degeneration or compression exerted by the arched ligament of the diaphragm. Mitral valve prolapse (MVP) is the most common valvular disorder. There are no reports on an association between CAS and MVP. METHODS: 1560 (41%) out of 3780 consecutive patients undergoing echocardiographic assessment of MVP, had Doppler sonography of the celiac tract to detect CAS. RESULTS: CAS was found in 57 (3.7%) subjects (23 males and 34 females) none of whom complained of symptoms related to visceral ischemia. MVP was observed in 47 (82.4%) subjects with and 118 (7.9%) without CAS (p < 0.001). The agreement between MVP and CAS was 39% (95% CI 32–49%). PSV (Peak Systolic Velocity) was the only predictor of CAS in MPV patients (OR 0.24, 95% CI 0.08–0.69) as selected in a multivariate logistic model. CONCLUSION: CAS and MVP seem to be significantly associated in patients undergoing consecutive ultrasonographic screening

Direct calibration of PICKY-designed microarrays

Abstract Background Few microarrays have been quantitatively calibrated to identify optimal hybridization conditions because it is difficult to precisely determine the hybridization characteristics of a microarray using biologically variable cDNA samples. Results Using synthesized samples with known concentrations of specific oligonucleotides, a series of microarray experiments was conducted to evaluate microarrays designed by PICKY, an oligo microarray design software tool, and to test a direct microarray calibration method based on the PICKY-predicted, thermodynamically closest nontarget information. The complete set of microarray experiment results is archived in the GEO database with series accession number GSE14717. Additional data files and Perl programs described in this paper can be obtained from the website http://www.complex.iastate.edu under the PICKY Download area. Conclusion PICKY-designed microarray probes are highly reliable over a wide range of hybridization temperatures and sample concentrations. The microarray calibration method reported here allows researchers to experimentally optimize their hybridization conditions. Because this method is straightforward, uses existing microarrays and relatively inexpensive synthesized samples, it can be used by any lab that uses microarrays designed by PICKY. In addition, other microarrays can be reanalyzed by PICKY to obtain the thermodynamically closest nontarget information for calibration

Shared probe design and existing microarray reanalysis using PICKY

<p>Abstract</p> <p>Background</p> <p>Large genomes contain families of highly similar genes that cannot be individually identified by microarray probes. This limitation is due to thermodynamic restrictions and cannot be resolved by any computational method. Since gene annotations are updated more frequently than microarrays, another common issue facing microarray users is that existing microarrays must be routinely reanalyzed to determine probes that are still useful with respect to the updated annotations.</p> <p>Results</p> <p><smcaps>PICKY</smcaps> 2.0 can design shared probes for sets of genes that cannot be individually identified using unique probes. <smcaps>PICKY</smcaps> 2.0 uses novel algorithms to track sharable regions among genes and to strictly distinguish them from other highly similar but nontarget regions during thermodynamic comparisons. Therefore, <smcaps>PICKY</smcaps> does not sacrifice the quality of shared probes when choosing them. The latest <smcaps>PICKY</smcaps> 2.1 includes the new capability to reanalyze existing microarray probes against updated gene sets to determine probes that are still valid to use. In addition, more precise nonlinear salt effect estimates and other improvements are added, making <smcaps>PICKY</smcaps> 2.1 more versatile to microarray users.</p> <p>Conclusions</p> <p>Shared probes allow expressed gene family members to be detected; this capability is generally more desirable than not knowing anything about these genes. Shared probes also enable the design of cross-genome microarrays, which facilitate multiple species identification in environmental samples. The new nonlinear salt effect calculation significantly increases the precision of probes at a lower buffer salt concentration, and the probe reanalysis function improves existing microarray result interpretations.</p

Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life

Acinic cell carcinoma in pregnancy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>We report an observational study on the etiology and recurrence of acinic cell carcinoma of the parotid gland that seemed to be related to pregnancy. The medical literature has never reported such an association; therefore, our case report is probably the first to mention this observation.</p> <p>Case presentation</p> <p>This report is of a 25-year-old Arabic female patient from the United Arab Emirates, who, during her first pregnancy, developed acinic cell carcinoma of the right parotid gland that was managed with surgical excision in the form of superficial parotidectomy. During her second pregnancy, which occurred four years later, she had a recurrence of the same malignant neoplasm associated with ipsilateral malignant cervical lymphadenopathy. The patient was managed with total parotidectomy and neck dissection, as well as postoperative adjuvant radiotherapy. Our observation on this particular case of acinic cell carcinoma is that the initial onset of her neoplasm was during her first pregnancy, and the recurrence of the same malignant disease was during a subsequent pregnancy. This chronologic association raised our suspicion that there might be a possible etiologic effect of pregnancy or its associated hormonal or physiologic changes or both on the pathogenesis or etiology of acinic cell carcinoma.</p> <p>Conclusion</p> <p>Some association might exist between pregnancy and the pathogenesis or etiology of acinic cell carcinoma.</p

Completeness and timeliness of tuberculosis notification in Taiwan

Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law in Taiwan. Several measures have been undertaken to improve reporting of TB but the completeness and timeliness of TB notification in Taiwan has not yet been systemically evaluated

Unfolding grain size effects in barium titanate ferroelectric ceramics

Grain size effects on the physical properties of polycrystalline ferroelectrics have been extensively studied for decades; however there are still major controversies regarding the dependence of the piezoelectric and ferroelectric properties on the grain size. Dense BaTiO3 ceramics with different grain sizes were fabricated by either conventional sintering or spark plasma sintering using micro- and nano-sized powders. The results show that the grain size effect on the dielectric permittivity is nearly independent of the sintering method and starting powder used. A peak in the permittivity is observed in all the ceramics with a grain size near 1μm and can be attributed to a maximum domain wall density and mobility. The piezoelectric coefficient d33 and remnant polarization Pr show diverse grain size effects depending on the particle size of the starting powder and sintering temperature. This suggests that besides domain wall density, other factors such as back fields and point defects, which influence the domain wall mobility, could be responsible for the different grain size dependence observed in the dielectric and piezoelectric/ferroelectric properties. In cases where point defects are not the dominant contributor, the piezoelectric constant d33 and the remnant polarization Pr increase with increasing grain size

Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease

COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease

Mucin Secretion Induced by Titanium Dioxide Nanoparticles

Nanoparticle (NP) exposure has been closely associated with the exacerbation and pathophysiology of many respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. Mucus hypersecretion and accumulation in the airway are major clinical manifestations commonly found in these diseases. Among a broad spectrum of NPs, titanium dioxide (TiO2), one of the PM10 components, is widely utilized in the nanoindustry for manufacturing and processing of various commercial products. Although TiO2 NPs have been shown to induce cellular nanotoxicity and emphysema-like symptoms, whether TiO2 NPs can directly induce mucus secretion from airway cells is currently unknown. Herein, we showed that TiO2 NPs (<75 nm) can directly stimulate mucin secretion from human bronchial ChaGo-K1 epithelial cells via a Ca2+ signaling mediated pathway. The amount of mucin secreted was quantified with enzyme-linked lectin assay (ELLA). The corresponding changes in cytosolic Ca2+ concentration were monitored with Rhod-2, a fluorescent Ca2+ dye. We found that TiO2 NP-evoked mucin secretion was a function of increasing intracellular Ca2+ concentration resulting from an extracellular Ca2+ influx via membrane Ca2+ channels and cytosolic ER Ca2+ release. The calcium-induced calcium release (CICR) mechanism played a major role in further amplifying the intracellular Ca2+ signal and in sustaining a cytosolic Ca2+ increase. This study provides a potential mechanistic link between airborne NPs and the pathoetiology of pulmonary diseases involving mucus hypersecretion