Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis

Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array-based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi-infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.     

整合患者导向的测量工具项目编制等距量表实现ICF类目用于评定的可操作化

目的通过整合不同的患者导向的测量工具的项目来编制ICF特定类目的等距量表结构。方法使用有效的122例类风湿关节炎患者的样本资料进行心理测量研究。患者完成6个不同的以患者导向的测量工具。将这些测量工具项目的内容与ICF类目进行匹配。对项目反应等级进行Rasch分析用于检查这些测量工具项目是否说明了ICF类目b130:能量和驱力功能,从而构成一个心理测量可靠的等距量表。结果 19个项目与b130能量和驱力功能有关。根据2χ检验和Z值统计,19个项目中的16个项目拟合Rasch模型(项目和个人的ZMean=0.451,ZSD=1.085和ZMean=-0.223,ZSD=1.132)。Person分离指数rβ是0.93。结论可以构建ICF类目等距量表使得单个ICF类目可操作化。每个项目的原始格式在等距量表中保持不变。本研究在ICF的操作和将来的实施方面迈出了重要的一步。     

The role of the sagittal view of the ductal arch in identification of fetuses with conotruncal anomalies using 4-dimensional ultrasonography.

OBJECTIVE: Conotruncal anomalies represent one fifth of all congenital heart defects (CHDs) detected in the fetus. However, the spatial relationship of the great vessels is incorrectly defined in about 20% of these cases. The sagittal view of the ductal arch is considered a standard ultrasonographic view in fetal echocardiography and can be easily visualized using 4-dimensional (4D) ultrasonography. This study was designed to determine the role of this ultrasonographic plane for the prenatal diagnosis of conotruncal anomalies. METHODS: We reviewed 4D volume data sets, acquired with the spatiotemporal image correlation technique, from fetuses with and without confirmed conotruncal anomalies. The visualization rate of the sagittal view of the ductal arch was compared among groups using standardized multiplanar views. RESULTS: This study included 183 volume data sets from fetuses in the following groups: (1) normal echocardiographic findings (n = 130); (2) conotruncal anomalies (n = 18); and (3) other CHDs (n = 35). Volumes of poor image quality were excluded from analysis (8.2% [15/183]). The visualization rate of the sagittal view of the ductal arch was significantly lower in fetuses with conotruncal anomalies (5.6% [1/18]) than that in fetuses without abnormalities (93.1% [108/116]) and that in fetuses with other CHDs (79.4% [27/34]; P < .01). Absence of visualization of the sagittal view of the ductal arch was associated with a likelihood ratio of 9.44 (95% confidence interval, 5.8-15.5) to have conotruncal anomalies. CONCLUSIONS: The sagittal view of the ductal arch may play an important role in the screening and prenatal diagnosis of conotruncal anomalies in 4D ultrasonography.     

Noninvasive testing for colorectal cancer: a review

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Endoscopic screening is now in favor and its use is increasing, but overall participation rates are poor. A substantial percentage of the population will likely continue to resist endoscopic screening. As such, a noninvasive biomarker for the early detection of CRC remains a priority. Herein, we (i) review the currently available noninvasive screening markers for the early detection of CRC, (ii) discuss newer markers that have undergone preliminary testing, and (iii) introduce and explain potentially promising markers of the future. METHODS: The published literature on markers for early detection of CRC was identified using a MEDLINE/PubMed search with secondary review of cited publications. RESULTS: Noninvasive testing for CRC is most advanced in testing for stool fecal occult blood, globin, or DNA mutations. Study of abnormal mucins has also been explored. Research for serum-based markers is just beginning and includes serum proteomics, nuclear matrix proteins, and serum DNA testing. CONCLUSIONS: Serial guaiac-based fecal occult blood testing (FOBT) is simple, inexpensive, and proven effective at reducing mortality from CRC. Immunochemical fecal occult blood tests facilitate compliance and offer improved specificity, but at increased cost in comparison to FOBT. Fecal DNA testing may provide enhanced sensitivity for detection of CRC in comparison with FOBT, but its high cost limits its use for generalized screening. Rectal mucin testing requires additional evaluation to determine its sensitivity and specificity in comparison with guaiac-based FOBT. Serum tests, such as proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy, but remain a hope for the future.     

Balloon dilatation of porcine bioprosthetic valves in the pulmonary position

Balloon dilatation (BD) of bioprosthetic valves was investigated in vivo and in vitro. Four children with stenotic bioprosthetic porcine valves in the pulmonary position underwent BD of the valve 10 to 24 months after its insertion. Average valve gradient was reduced from 47.5 to 27 mm Hg. Obstruction at the conduit-branch pulmonary artery connection became apparent after dilatation of the valve. These distal stenoses were also dilated. BD technique was tested in vitro with the use of nonstenotic valves in fresh conduits. No damage to the valve or to the conduit was found when oversized balloons were used in a standard fashion or intentionally inflated until rupture. It is concluded that conduit replacement may be deferred by balloon dilatation of obstructed biological valves and/or a stenotic conduit-pulmonary artery anastomosis.     

Identification of components of a phosphoinositide signaling pathway in retinal rod outer segments

Phototransduction in retinal rods involves a G protein-coupled signaling cascade that leads to cGMP hydrolysis and the closure of cGMP-gated cation channels that are open in darkness, producing a membrane hyperpolarization as the light response. For many years there have also been reports of the presence of a phosphoinositide pathway in the rod outer segment, though its functions and the molecular identities of its components are still unclear. Using immunocytochemistry with antibodies against various phosphoinositide-specific phospholipase C (PLC) isozymes (β1–4, γ1–2, and δ1–2), we have found PLCβ4-like immunoreactivity in rod outer segments. Similar experiments with antibodies against the α-subunits of the G_q family of G proteins, which are known to activate PLCβ4, have also demonstrated G_α11-like immunoreactivity in this location. Immunoblots of total proteins from whole retina or partially purified rod outer segments with anti-PLCβ4 and anti-G_α11 antibodies gave, respectively, a single protein band of the expected molecular mass, suggesting specific labelings. The retinal locations of the two proteins were also supported by in situ hybridization experiments on mouse retina with probes specific for the corresponding mouse genes. These two proteins, or immunologically identical isoforms, therefore likely mediate the phosphoinositide signaling pathway in the rod outer segment. At present, G_α11 or a G_α11-like protein represents the only G protein besides transducin (which mediates phototransduction) identified so far in the rod outer segment. Although absent in the outer segment layer, other PLC isoforms as well as G_αq (another G_q family member), are present elsewhere in the retina.     

The clinical evolution of Lyme arthritis

To determine the clinical evolution of Lyme arthritis, 55 patients who did not receive antibiotic therapy for erythema chronicum migrans were followed longitudinally for a mean duration of 6 years. Of the 55 patients, 11 (20%) had no subsequent manifestations of Lyme disease. From 1 day to 8 weeks after disease onset, 10 of the patients (18%) began to have brief episodes of joint, periarticular, or musculoskeletal pain for as long as 6 years, but they never developed objective joint abnormalities. From 4 days to 2 years after disease onset, 28 (51%) had one episode or began to have intermittent attacks of frank arthritis, primarily in large joints; a few had polyarticular movement. The total number of these patients who continued to have recurrences decreased by 10% to 20% each year. The remaining 6 patients (11%) developed chronic synovitis later in the illness; of these, 2 (4%) had erosions, and 1 (2%), permanent joint disability. The spectrum of Lyme arthritis ranges from subjective joint pain, to intermittent attacks of arthritis, to chronic erosive disease.     

Predictors of advanced proximal neoplasia in persons with abnormal screening flexible sigmoidoscopy.

BACKGROUND & AIMS: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. RESULTS: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>or=10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. CONCLUSIONS: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia.