Serum contains a potent factor that decreases β-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes

L-type Ca²⁺ current (I _Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I _Ca induced by -adrenergic stimulation (isoprenaline 2· 10^–7 M) could be completely antagonized by diluted sera (1100 v/v). Half-maximal inhibition of -receptorstimulated I _Ca occurred at about 11000. Basal I _Ca was not affected by serum. Atropine in a concentration (10^–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10^–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10^–4 M) pipette solution, potentiated I _Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits -receptor-stimulated adenylyl cyclase via G_iprotein.A preliminary report of this work has appeared in abstract form [11]     

Osteotomy around the knee: Assessment of quality,content and readability of online information

BackgroundAs knee osteotomy surgery becomes increasingly accessible, more patients may turn to the Internet for information. This study examined the source, quality, content and readability of online information regarding osteotomy around the knee.MethodsThe first 70 websites returned by the top four search engines were identified using the key words: “knee osteotomy” and “high tibial osteotomy.” The websites were categorised by type and assessed using the DISCERN score, Journal of the American Medical Association (JAMA) benchmark criteria and a novel Knee Osteotomy-Specific Score (KOSS). The presence of the Health On the Net (HON) code accreditation seal was noted. Readability of each website was assessed using eight readability formulae. The mean reading grade level (RGL) was compared to the 6th and 8th grade reading levels. The mean RGL of each category was also compared.ResultsOf the 45 unique websites analysed, the majority were Physician (33%) and Journal websites (31%). The mean DISCERN score was 36.7 (±8.9) which is classified as ‘poor.’ The mean JAMA benchmark criteria score was 2.04 (±1.5) and Physician websites were most likely to be scored zero. The mean KOSS was 15.4 (±5.7). The highest scoring website was a Commercial site but, overall, Journal category sites provided the best quality information. Websites that bore the HONcode seal obtained higher DISCERN, JAMA benchmark criteria and Knee Osteotomy - Specific Scores.The cumulative mean RGL was 13.2 (±2.2) which exceeded the 6th grade level by an average of 7.2 grade levels and the 8th grade level by an average of 5.2 grade levels. No website (0%) was written at or below either the 6th or the 8th grade reading levels. The mean Flesch Reading Ease Score of all websites was 41.13 (±14.7) which is classified as ‘difficult.’ Journal websites had the highest RGL.ConclusionThe information available online regarding osteotomy around the knee varies tremendously in quality and completeness. Physician sites predominate, but these were among the lowest scoring of all websites. Even where high quality information is available, it is set at too high a level to be easily understood.Level of evidenceSurvey of materials – Internet.     

CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

优化的贴片型测量探头及其生物医学应用研究

采用时域有限差分（FDTD）法结合遗传算法（GA）优化设计了适用于浅表生物组织高频测量的宽带同轴贴片探头，并用该探头测量了人体背部1～7GHz频带内的反射特性。优化设计出的圆形同轴贴片探头具有轴对称特点，辐射近场在生物组织中透人深、反射系数的频率响应特性好。所获得的人体背部反射特性的测量结果将为背部浅表组织电特性的重建提供有利的依据。     

Visualizing metabolic changes in breast-cancer tissue using 1H-NMR spectroscopy and self-organizing maps

In-vitro NMR spectroscopic examinations of tissue extracts can be combined with appropriate pattern-recognition and visualization techniques in order to monitor characteristic metabolic differences between tissue classes. In the present study, such techniques are applied to a set of 88 breast-tissue samples with the intention of identifying typical differences between various tissue classes. The set contains 49 breast-tumor samples of various tumor grades and 39 samples of healthy tissue. The metabolite compositions of the tissue extracts were investigated using a dual extraction technique and high-resolution (1)H-NMR spectroscopy. The spectra of the hydrophilic and the lipophilic compounds were assigned to three groups according to different malignancy grades of the respective tissue samples. The group characteristics were analyzed using the k-nearest-neighbor method and self-organizing-map visualizations. The results show an increase of UDP-hexose, phosphocholine and phosphoethanolamine concentrations according to the tumor grade. Higher concentrations of taurine were detected in the malignant samples. Myo-inositol and glucose content were elevated in control samples compared with malignant tissue. Both compounds also characterized different subgroups in the pool of unaffected tissue samples depending upon fat content or fibrosis. Several lipid metabolites showed a characteristic elevation with high malignancy.     

Cloning of the PYR4 gene encoding orotidine-5′-phosphate decarboxylase in Cephalosporium acremonium

Summary We have cloned the Cephalosporium acremonium pyr4 gene by cross-hybridization with the equivalent gene from Neurospora crassa, the closest relative from which this gene is available. The C. acremonium pyr4 gene complements an E. coli pyrF mutant lacking orotidine-5-phosphate decarboxylase (OMPdecase), and most probably does not contain introns. Maxicell analysis in E. coli shows that it encodes a 46 kDa polypeptide. The C. acremonium OMPdecase contains a highly conserved pentadecapeptide characteristic for this category of enzyme. Extensive sequence comparison suggests an important role of this region in enzymatic activity.     

PLPP2: Potential therapeutic target of breast cancer in PLPP family

PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.     

Systemic Administration of Immunostimulatory DNA Sequences Mediates Reversible Inhibition of Th2 Responses in a Mouse Model of Asthma

This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.     

Fine Mapping Functional Sites or Regions from Case-Control Data Using Haplotypes of Multiple Linked SNPs

Previously, we reported an algorithm for scanning a large number of tightly linked single nucleotide polymorphisms (SNPs) for LD mapping of functional sites or regions from a family‐based association design. In the present study, we extend our method to a case‐control design. We first use the expectation maximization (EM) algorithm to estimate haplotype frequencies of multiple linked SNPs, and follow this by constructing a contingency table statistic S for LD analysis, based on the estimated haplotype frequencies. An empirical p‐value is obtained based on the null distribution of the maximum of S (S *) from a large number (e.g., 1,000 or more) of randomized permutations. The proposed algorithm has been implemented in a computer program in which window searching for functional SNP sites can cover any number of loci without limitation, except that of computer storage. Unlike other programs for a case‐control design that always conduct tests at a fix window width, in our program after setting a maximum size of haplotype window width, for a given maximum window width all possible widths of haplotypes are utilized to find the maximum statistic S * for each locus under investigation. The sensitivity of the proposed algorithm has been examined with simulated and real genotyping datasets. Association analyses indicate that our program is powerful enough to detect most, if not all, functional SNPs simulated in the original model or identified in the original report. Moreover, the program is very flexible and can be used in either regional or genome‐wide scanning for association analysis with SNP markers.     

Nonlinearity identified by neural network models inP CO 2 control system in humans

The nonlinearity included in the P_{CO 2} control system in humans is evaluated using the degree of nonlinearity based on a difference of residuals. An autoregressive moving average (ARMA) model and neural networks (linear and nonlinear) are employed to model the system, and three types of network (Jordan, Elman and fully interconnected) are compared. As the Jordan-type linear network cannot approximate respiratory data accurately, the other two types and the ARMA model are used for the evaluation of the nonlinearity. The results of the evaluation indicate that the linear assumption for the P_{CO 2} control system is invalid for three subjects out of seven. In particular, strong nonlinearity was observed for two subjects.