Bacterial adhesion to titanium-oxy-nitride (TiNOX) coatings with different resistivities: a novel approach for the development of biomaterials

In this study the quantitative adhesion of a strain of Staphylococcus epidermidis, Streptococcus mutans and Pseudomonas aeruginosa to and the ease of removal from different TiNOX coatings was investigated by means of a parallel plate flow chamber and in situ image analysis. Quality of adhesion was determined by counting bacteria which remained attached to the surface after exposure to an air-liquid interface. S. epidermidis and S. mutans showed a bipolar adhesion pattern with highest numbers of adhesion at low and high resistivity with lowest adhesions at a resistivity of 10(4) microohms cm. P. aeruginosa was the least adherent organism. These results indicate that the affinity of these three strains under the current experimental conditions is minimal for TiNOX coatings with a specific resistivity. TiNOX coatings with pre-adsorbed fibrinogen showed different numbers of S. epidermidis adhered to the different coatings. However, the affinity of this strain for fibrinogen-coated TiNOX remains low when the resistivity is around 10(4) microohms cm. This indicates that the specific influence of the resistivities of the TiNOX coatings is transferred through the adsorbed fibrinogen film to the interface with adhering bacteria.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA

We have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue- specific expression and regulation of CFTR function when animal models are used in gene therapy studies.      

Epithelial proliferations of ductal type

The diagnosis of ductal proliferations requires analysis of both architectural and cytological features. Architectural characteristics of conventional ductal hyperplasia include persistence of the duct lumen as peripheral, crescent shaped spaces; streaming of cells; formation of irregular, slit-like fenestrations; and "maturation." Hyperplastic ductal cells exhibit indistinct cell borders, irregular placement of nuclei, irregular nuclear shapes, granular chromatin, and uniform small nucleoli. The cells do not show polarization or dishesion. Low-grade ductal carcinoma in-situ exhibits both architectural and cytological atypicality. The architectural atypicality takes two forms: the formation of cribriform spaces or their variants and the regular arrangement of cells. The former reflects the polarization of the carcinoma cells and the latter their dishesion. Cytological atypicality includes distinct cell borders; smoothly contoured, oval or round nuclei; homogeneous chromatin; and inconspicuous nucleoli. Atypical ductal hyperplasia shows low-grade cytological atypicality but lacks the architectural atypicality of ductal carcinoma in situ. Proliferations lacking cytological atypicality do not merit the diagnosis of atypical ductal hyperplasia whatever their architectural characteristics. Although not usually necessary, immunohistochemical staining for high molecular weight keratin can help resolve difficult cases. Current evidence does not support the belief that conventional ductal hyperplasia represents an obligate precursor to ductal carcinoma in situ.     

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

Uncommon morphologic patterns of lobular neoplasia.

Discussions of the morphology of lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in-situ) usually emphasize the commonplace characteristics. Occasional cases deviate from the expected appearance and thereby cause diagnostic confusion. Unusual cytologic alterations include the formation of signet-ring cells and the presence of nuclear pleomorphism. The growth of lobular neoplasia in breast tissue altered by atrophy, sclerosing adenosis, collagenous spherulosis, and benign tumors gives rise to unexpected patterns that one might mistake for normal tissue, invasive carcinoma, or ductal carcinoma in situ. Solid involvement of ducts by lobular neoplasia and uncommon forms of "pagetoid" growth both resemble the appearance of atypical ductal hyperplasia or ductal carcinoma in situ. The authors illustrate these unusual cytologic and architectural findings and discuss features that permit proper diagnosis and interpretation.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

原发性单侧症状帕金森病磁共振氢质子谱研究

目的:探讨磁共振氢质子谱(1H-MRS)对原发性单侧起病帕金森病的诊断价值。方法:未经治疗的原发单侧症状PD患者50例为PD组,健康人42名为对照组。两组分别予以双侧壳核MRS检查,由仪器自带软件自动计算得双侧壳核代谢物比值:NAA/Cr,Cho/Cr,NAA/Cho。结果:PD组患者其症状对侧壳核NAA/cr比值分别较同侧及健康对照组双侧壳核相应比值均值明显下降(分别为1.23±0.22,1.38±0.33,1.33±0.16;t=2.616,P=0.01和t=2.324,P=0.02),而其NAA/Cho、Cho/Cr比值较同侧及对照组相应比值均值无显著差异。症状同侧壳核NAA/cr、NAA/Cho、Cho/Cr较对照组无明显差异。结论:原发性单侧症状PD其症状的对侧壳核早期就可能存在神经元的缺失或胶质增生,提示壳核磁共振波谱分析可为早期PD的临床诊断提供较为可靠的客观依据。     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.