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Juha-Matti Savola Michael Hill Mia Engstrom Hannele Merivuori Siegfried Wurster Steven G McGuire Susan H Fox Alan R Crossman Jonathan M Brotchie 《Movement disorders》2003,18(8):872-883
Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease. 相似文献
23.
W P Vaughan J D Dennison E C Reed L Klassen T R McGuire W G Sanger P P Kumar P I Warkentin B G Gordon P J Bierman 《Bone marrow transplantation》1991,8(6):489-495
Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02). 相似文献
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Controlled release of sugar and toxicant from a novel device for controlling pest insects 总被引:1,自引:0,他引:1
Xing Ping Hu Baruch S. Shasha Michael R. McGuire Ronald J. Prokopy 《Journal of controlled release》1998,50(1-3):257-265
A novel biodegradable device, designed for long-lasting residual effectiveness of feeding stimulant (sugar) and insecticide (dimethoate) against apple maggot flies and other insects, was formulated. The device is an 8-cm diameter fruit-mimicking sphere, consisting of 42–50% sugar entrapped in a mixture of gelatinized corn flour and wheat flour in the presence of glycerin, and coated with a layer of latex paint containing dimethoate and sugar. We found that the outer layer of paint prevents cracking of the sphere upon drying and creates a barrier to control the release of both sugar and dimethoate. Releases of each ingredient were screened first by chemical analysis and then by bioassays in the laboratory and in field cages against apple maggot flies. Chemical analysis demonstrated strong potential for controlled release of water-soluble feeding stimulant and water-insoluble insecticide measured as a function of the amount of rainfall and duration of exposure time. Field results showed greater than 70% insecticidal activity after 11 weeks of sphere exposure in an orchard. This device has the potential to be used for a variety of insect-control applications through manipulating its shape, color and texture into forms known to be attractive to target insects, and by employing various toxicants designed to be effective against such insects. 相似文献
26.
Bilateral hydroureteronephrosis following ileal conduit urinary diversion is not uncommon. It may be owing to ureteroileal stenosis, stomal stenosis or a poorly compliant ileal conduit. The standard evaluation of stoma size, conduit residual urine and a loopogram often fail to allow determination of the cause of ureteral dilatation. In addition to these standard tests, we have used conduit urodynamics to study conduit function with a triple lumen urodynamic catheter to measure simultaneously conduit pressure proximal and distal to the fascia during filling under fluoroscopy. In 4 control patients with normal upper tracts who were studied with this technique conduit leak point pressures ranged from 5 to 20 cm. water pressure. Six patients with bilateral hydroureteronephrosis were studied to evaluate conduit function. We found abnormalities in 5 patients, including functional stomal stenosis in 2, an atonic loop in 1, segmental obstruction in 1 and a high pressure noncompliant distal segment in 1. 相似文献
27.
T G McGuire B Dickey G E Shively I Strumwasser 《The American journal of psychiatry》1987,144(5):616-620
Specialized psychiatric facilities, including qualified distinct-part units in general hospitals, are exempt from Medicare's diagnosis-related group prospective payment system (PPS). One major reason for continuing the exemption is the redistribution of revenue that would probably occur if a single national price were established for care at the diverse facilities that treat patients with psychiatric and substance abuse disorders. This study investigated the extent of such potential redistribution in a private health insurance data base and found that a PPS would systematically underpay specialized facilities and systematically overpay general hospitals without specialized units. Alternatives for addressing this problem are discussed. 相似文献
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A cDNA for the estradiol-regulated 24K protein: Control of mRNA levels in MCF-7 cells 总被引:1,自引:0,他引:1
Ines Moretti-Rojas Suzanne A. W. Fuqua Robert A. Montgomery III William L. McGuire 《Breast cancer research and treatment》1988,11(2):155-163
We have previously demonstrated an estradiol-regulated 24 kDa (24K) protein in human breast cancer tissue culture cells and human tumor biopsies. The presence of 24K correlates well with the presence of steroid hormone receptors. In order to further study the hormonal regulation of the 24K protein and gene, we have isolated cDNA clones corresponding to the 24K mRNA.Poly(A)+ RNA isolated from the MCF-7 human breast cancer cell line was translated in a cell-free translation system containing [35S]-methionine. The translation products were immunoprecipitated with a 24K monoclonal antibody, and thein vitro synthesis of 24K protein was confirmed by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis. The same poly(A)+ RNA was used to construct an oligo(dT)-primed cDNA library in thegt11 expression vector system. The library was screened with a highly specific polyclonal antibody raised against 24K protein purified by immunoaffinity chromatography. Four recombinant clones reacting with the antibody by virtue of antigen expression were isolated and three were used in hybridization-selected translation. Three clones were able to hybridize specifically to a messenger RNA (mRNA) that yielded a Mr 24,000 protein when translatedin vitro and analyzed by SDS/polyacrylamide gel electrophoresis. This protein was also immunoprecipitable by the 24K monoclonal antibody. MCF-7 mRNA size fractionated by formaldehyde-agarose gel electrophoresis was transferred to nitrocellulose paper and hybridized to a nick-translated 24K cDNA clone. A single band of hybridization corresponding to a mRNA size of approximately 0.9–1.0 kilobase (kb) was observed. Using this same technique, 24K cDNA was hybridized to mRNA extracted from MCF-7 cells that had been treated for varying periods with either estradiol, nafoxidine, or tamoxifen. The 24K mRNA was elevated by the addition of estradiol, and clearly diminished by nafoxidine and tamoxifen.These results demonstrate that we have isolated cDNA clones for the study of the hormonal regulation of the 24K gene in breast cancer cells, and have shown that the mRNA is regulated by estradiol. 相似文献
30.
Characterization of an immunoprotective protein complex of Anaplasma marginale by cloning and expression of the gene coding for polypeptide Am105L. 总被引:4,自引:13,他引:4
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Immunization with an Anaplasma marginale surface protein complex containing two polypeptides (Am105U and Am105L), each having a molecular weight of 105,000, protected cattle against challenge with virulent organisms. These polypeptides were immunoprecipitated together from detergent extracts of A. marginale by a neutralizing monoclonal antibody. After surface radioiodination of intact parasites, both Am105U and Am105L contained the radiolabel. To define the structural and antigenic relationships between Am105U and Am105L and to determine individual efficacies as protective immunogens, we cloned and expressed A. marginale DNA in Escherichia coli. We identified recombinant bacteria which expressed a novel protein of 105,000 molecular weight as a major cellular component. The recombinant protein was structurally and antigenically homologous to Am105L. There were multiple, partially homologous copies of the cloned DNA sequence in the rickettsial genome. 相似文献