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61.
Antibodies were raised against specific peptides from N-terminal regions of the alpha1 and alpha3 isoforms of the GABA(A) receptor, and used to assess the relative expression of these proteins in the superior frontal and primary motor cortices of 10 control, nine uncomplicated alcoholic and six cirrhotic alcoholic cases were matched for age and post-mortem delay. The regression of expression on post-mortem delay was not statistically significant for either isoform in either region. In both cortical areas, the regression of alpha1 expression on age differed significantly between alcoholic cases, which showed a decrease, and normal controls, which did not. Age had no effect on alpha3 expression. The alpha1 and alpha3 isoforms were found to be expressed differentially across cortical regions and showed a tendency to be expressed differentially across case groups. In cirrhotic alcoholics, alpha1 expression was greater in superior frontal than in motor cortex, whereas this regional difference was not significant in controls or uncomplicated alcoholics. In uncomplicated alcoholics, alpha3 expression was significantly lower in superior frontal than in motor cortex. Expression of alpha1 was significantly different from that of alpha3 in the superior frontal cortex of alcoholics, but not in controls. In motor cortex, there were no significant differences in expression between the isoforms in any case group. 相似文献
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63.
BMPs as mediators of roof plate repulsion of commissural neurons 总被引:1,自引:0,他引:1
During spinal cord development, commissural (C) neurons, located near the dorsal midline, send axons ventrally and across the floor plate (FP). The trajectory of these axons toward the FP is guided in part by netrins. The mechanisms that guide the early phase of C axon extension, however, have not been resolved. We show that the roof plate (RP) expresses a diffusible activity that repels C axons and orients their growth within the dorsal spinal cord. Bone morphogenetic proteins (BMPs) appear to act as RP-derived chemorepellents that guide the early trajectory of the axons of C neurons in the developing spinal cord: BMP7 mimics the RP repellent activity for C axons in vitro, can act directly to collapse C growth cones, and appears to serve an essential function in RP repulsion of C axons. 相似文献
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65.
OBJECTIVE: To identify key diagnostic cytologic criteria for various low grade spindle cell lesions. STUDY DESIGN: We reviewed 20 synovial sarcomas, 18 benign neural tumors, 10 reparative lesions, 24 other benign and 27 additional malignant low grade spindle cell lesions. All specimens were coded as to the presence or absence of the following variables: high cellularity, tissue fragments, tissue culture appearance, epithelial fragments, vessel fragments, vascular arcades, fibrillar ground substance, myxoid background, microcystic areas, parallel arrangement of nuclei, naked nuclei, single cells, binucleate cells, multinucleate cells, long filamentous cells, short spindle cells, stellate cells, lipoblasts, nuclear pleomorphism, nuclei with pointed ends, comma/fishhook nuclei, cigar-shaped nuclei, ovoid/round nuclei, small nucleoli, large nucleoli, mitotic figures, intranuclear vacuoles and background histiocytes. A logistic regression analysis was performed to identify the variables predictive of malignant lesions, specifically synovial sarcomas, benign neural tumors and reparative lesions. RESULTS: Statistical analysis selected high cellularity, short spindle cells, small nucleoli and absence of tissue culture appearance as the main criteria for malignant neoplasms. Tissue fragments and high cellularity were selected as the primary criteria and absence of long filamentous cells and of myxoid background as the secondary criteria for synovial sarcomas. It selected fibrillar ground substance and absence of ovoid/round nuclei as the key criteria for benign neural tumors. The presence of a tissue culture appearance was the major criterion for reparative lesions. CONCLUSION: There are many previously described cytologic criteria, but we found that when subjected to statistical analysis, only a few features were significant in the evaluation of low grade spindle cell lesions. 相似文献
66.
BACKGROUND: Goblet cells in the lower respiratory tract are metaplastic bronchial epithelial cells usually associated with asthma or chronic bronchitis. Goblet cells acquire their name by a tendency to distend with mucus, with subsequent distortion in cell shape. Due to similarity of shape, metaplastic goblet cells and signet ring cells can be easily confused in cytologic samples. CASE: A 55-year-old male with a history of gastrointestinal adenocarcinoma underwent brushing, washing and biopsy of a bronchial lesion. The bronchial wash and brush samples showed a very cellular specimen, with large aggregates of distended columnar cells. These were arranged in long strips, thick bundles and occasional three-dimensional aggregates. Some aggregates contained numerous rounded cells with markedly distended cytoplasm. The rounded cells were slightly larger than the distended columnar cells. These cells had a relatively large but innocuous-appearing nucleus displaced to the periphery of the cell. The corresponding bronchial biopsy revealed signet ring adenocarcinoma, presumably metastatic from the gastrointestinal primary. CONCLUSION: Signet ring adenocarcinoma, either primary or metastatic, can be difficult to diagnose in cytologic and histologic specimens. There are numerous mimics of signet ring cells, both benign and neoplastic. In respiratory cytologic specimens, one of the benign imposters is goblet cell metaplasia. 相似文献
67.
A gene encoding a deoxyribonuclease, dnsH, was cloned from Aeromonas hydrophila JMP636. The predicted mature protein was very similar to the previously described extracellular Dns from this organism and an N-terminal region corresponding to a large putative signal sequence was predicted for the JMP636 protein. Inactivation of dnsII demonstrated that the DnsH protein was not present extracellularly in this strain. As DnsH degraded plasmid DNA and was believed to have a periplasmic location, a dnsH mutant was constructed to determine whether electroporation of A. hydrophila with plasmid DNA could be achieved. No transformants were detected. From SDS-PAGE studies, at least two additional DNases remain to be characterised from A. hydrophila JMP636. 相似文献
68.
Kessler A Faure H Petrel C Ruat M Dauban P Dodd RH 《Bioorganic & medicinal chemistry letters》2004,14(12):3345-3349
The synthesis and calcimimetic activities of two new families of compounds are described. The most active derivatives of the first family, N(2)-(2-chloro-(or 4-fluoro-)benzyl)-N(1)-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamine (4b and 4d, respectively, tested at 10 microM) produced 98+/-6% and 95+/-4%, respectively, of the maximal stimulation of [(3)H]inositol phosphates production obtained by 10mM Ca(2+) in CHO cells expressing the rat calcium sensing receptor (CaSR). The second family of calcimimetics was obtained by conformationally restraining the compounds of type 4 to provide the 2-aminomethyl derivatives 5. One of these compounds, (R)-2-[N-(1-(1-naphthyl)ethyl)aminomethyl]indole ((R)-5a, calindol), displayed improved calcimimetic activity compared to 4b and 4d as well as stereoselectivity. In the presence of 2mM Ca(2+), calindol stimulated [(3)H]inositol phosphates accumulation with an EC(50) of 1.0+/-0.1 or 0.31+/-0.05 microM in cells expressing the rat or the human CaSR, respectively. The calcimimetic activities of these novel compounds were shown to be due to a specific interaction with the CaSR. 相似文献
69.
Bowen BW Bass AL Chow SM Bostrom M Bjorndal KA Bolten AB Okuyama T Bolker BM Epperly S Lacasella E Shaver D Dodd M Hopkins-Murphy SR Musick JA Swingle M Rankin-Baransky K Teas W Witzell WN Dutton PH 《Molecular ecology》2004,13(12):3797-3808
Juvenile loggerhead turtles (Caretta caretta) from West Atlantic nesting beaches occupy oceanic (pelagic) habitats in the eastern Atlantic and Mediterranean, whereas larger juvenile turtles occupy shallow (neritic) habitats along the continental coastline of North America. Hence the switch from oceanic to neritic stage can involve a trans-oceanic migration. Several researchers have suggested that at the end of the oceanic phase, juveniles are homing to feeding habitats in the vicinity of their natal rookery. To test the hypothesis of juvenile homing behaviour, we surveyed 10 juvenile feeding zones across the eastern USA with mitochondrial DNA control region sequences (N = 1437) and compared these samples to potential source (nesting) populations in the Atlantic Ocean and Mediterranean Sea (N = 465). The results indicated a shallow, but significant, population structure of neritic juveniles (PhiST = 0.0088, P = 0.016), and haplotype frequency differences were significantly correlated between coastal feeding populations and adjacent nesting populations (Mantel test R2 = 0.52, P = 0.001). Mixed stock analyses (using a Bayesian algorithm) indicated that juveniles occurred at elevated frequency in the vicinity of their natal rookery. Hence, all lines of evidence supported the hypothesis of juvenile homing in loggerhead turtles. While not as precise as the homing of breeding adults, this behaviour nonetheless places juvenile turtles in the vicinity of their natal nesting colonies. Some of the coastal hazards that affect declining nesting populations may also affect the next generation of turtles feeding in nearby habitats. 相似文献
70.
Structure, activity and evolution of the group I thiolactone peptide quorum-sensing system of Staphylococcus aureus 总被引:4,自引:0,他引:4
MDowell P Affas Z Reynolds C Holden MT Wood SJ Saint S Cockayne A Hill PJ Dodd CE Bycroft BW Chan WC Williams P 《Molecular microbiology》2001,41(2):503-512
In Staphylococcus aureus, the agr locus is responsible for controlling virulence gene expression via quorum sensing. As the blockade of quorum sensing offers a novel strategy for attenuating infection, we sought to gain novel insights into the structure, activity and turnover of the secreted staphylococcal autoinducing peptide (AIP) signal molecules. A series of analogues (including the L-alanine and D-amino acid scanned peptides) was synthesized to determine the functionally critical residues within the S. aureus group I AIP. As a consequence, we established that (i) the group I AIP is inactivated in culture supernatants by the formation of the corresponding methionyl sulphoxide; and (ii) the group I AIP lactam analogue retains the capacity to activate agr, suggesting that covalent modification of the AgrC receptor is not a necessary prerequisite for agr activation. Although each of the D-amino acid scanned AIP analogues retained activity, replacement of the endocyclic amino acid residue (aspartate) located C-terminally to the central cysteine with alanine converted the group I AIP from an activator to a potent inhibitor. The screening of clinical S. aureus isolates for novel AIP groups revealed a variant that differed from the group I AIP by a single amino acid residue (aspartate to tyrosine) in the same position defined as critical by alanine scanning. Although this AIP inhibits group I S. aureus strains, the producer strains possess a functional agr locus dependent on the endogenous peptide and, as such, constitute a fourth S. aureus AIP pheromone group (group IV). The addition of exogenous synthetic AIPs to S. aureus inhibited the production of toxic shock syndrome toxin (TSST-1) and enterotoxin C3, confirming the potential of quorum-sensing blockade as a therapeutic strategy. 相似文献