Biomedical subjects
Publications and source records attributed to M Clinton.
Parathymosin is a 101-amino acid polypeptide involved in the regulation of cellular immunity. In situ hybridization of rat parathymosin cDNA to human metaphase chromosomes localized the gene for human parathymosin to the q12----q22 region of chromosome 17.
Parathymosin has been purified from calf liver and its primary sequence established, except for a segment containing approximately 11 amino acid residues in the central part of the polypeptide chain. Bovine parathymosin contains approximately 101 amino acid residues and shows 90% identity with rat parathymosin, with substitution of Glu for Asp at positions 21, 57, and 58, Asp for Glu at positions 60 and 63, and Ala for Val at position 77. Three non-conservative substitutions were Ala for Thr at position 81, Leu for Arg at position 78, and Val for Lys at position 79. The replacement at the last two positions of a pair of basic by hydrophobic amino acid residues may account for differences in chromatographic behavior observed for the bovine and rat polypeptides. Analysis of the NH2-terminus employed a new deblocking procedure which was also employed to analyze rat parathymosin, requiring correction of the previously published NH2-terminal sequence for that polypeptide.
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A rat spleen cDNA library was screened for clones carrying the cDNAs for prothymosin alpha and parathymosin. Sequence analysis of a clone carrying the entire coding region for prothymosin alpha confirmed and completed the amino acid sequence for this polypeptide and established the number of amino acid residues as 111. Rat prothymosin alpha differs from human prothymosin alpha at six positions, including four substitutions and two insertions. The nucleotide sequences of the cDNAs for the rat and human polypeptides are more than 90% identical in the open reading frames, with significant homology extending into the 5' and 3' flanking regions. From the same library, we also isolated a clone carrying 80% of the coding region for rat parathymosin. The number of amino acid residues in rat parathymosin is 101, based on the sequence deduced from the cDNA insert and earlier information on the sequence in the amino-terminal portion of this polypeptide. Despite their similarity in size and amino acid composition, rat prothymosin alpha and rat parathymosin show only limited sequence homology, primarily in the segment including residues 14 through 25, where 10 of 12 positions are identical in the two polypeptides. this is also the region of significant sequence similarity to a 12-amino-acid segment in the p17 protein of the human immunodeficiency disease associated virus (HTLV-IIIB).
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The mast cell activator, compound 48/80, produced increased vascularity and tortuosity of blood vessels in the chorioallantoic membrane (CAM) of ten day old embryonic chicks. Application of 400 micrograms/ml resulted in rapid mast cell granule release, observed after 1 min at both light and electron microscopy level, and resulted in the greatest increase (69%) in CAM mesenchymal vessels. The half-maximal dose was 38.6 micrograms/ml, computer-derived from the dose-response data. It is apparent that a single episode of mast cell degranulation is sufficient to induce vessel growth over several days, but the fact that a sublethal dose is required for maximum stimulation casts doubt on its biological significance. This pattern of response resembles that previously found by us with histamine and has not been found so far with commercial heparins and chemically modified derivatives. In contrast, a sublethal dose of porcine intestinal sodium heparin results in an antiangiogenic effect on the ectodermal capillary plexus.
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Forty-eight consecutive applicants and 30 known clonidine-abusing methadone patients at three methadone treatment programs were surveyed regarding their use of clonidine. Two distinct patterns of clonidine use emerged. Of 22 applicants who took clonidine illicitly, 15 used it primarily to decrease opioid withdrawal, as well as for its sedating effect. Applicants mostly obtained it from physicians, used an average dose of 0.37 mg at a time, and about one third believed clonidine to be addictive. In contrast, clonidine-using patients took clonidine primarily for its psychoactive effects, including the interaction with methadone, in addition to decreasing opioid withdrawal. Patients obtained clonidine frequently on the street and from family or friends, but less from physicians. The average reported dose for patients was 0.6 mg. The vast majority of these patients felt clonidine was addictive. Our findings, when coupled with the risk inherent in clonidine overdose, suggest that further research into the identification and treatment of clonidine abuse among methadone patients is warranted.
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The radiology department at Dartmouth Hitchcock Medical Center (DHMC) adopted a just-in-time (JIT) inventory management system in 1992, reducing the volume of its in-house inventory of radiology supplies from a value of $400,000 to $16,000, just enough for four to five days of activity. An asset manager, the only person authorized to order supplies, was given responsibility for maintaining the department's supply of fixed and consumable assets. The first step in implementing the new system was to identify the supplies needed, standardize them and determine how often deliveries would be made. The JIT implementation team developed a request for proposal (RFP) that incorporated the standardized list of supplies. Three radiology supply vendors were invited to respond to the RFP. The team later determined that only one vendor was capable of implementing the JIT program. A three-year contract was awarded to that vendor. As that three-year contract reached completion, DHMC offered the JIT program to its eight affiliate hospitals and four outpatient clinics. The team decided to re-bid the contract for the entire network, which collectively performed 700,000 radiology exams annually. The new RFP encompassed 90 percent of the network's consumable supplies and offered customized delivery for each facility. The team identified eight criteria necessary for the evaluation of each vendor response to the RFP, rather than use price as the only consideration. The company that won the three-year contract furnished 90 percent of the radiology supplies for the DHMC network, allowing even further savings by the network, particularly for the smaller facilities and clinics. The program is continually monitored, adjusted and enhanced in order to incorporate changing departmental needs.
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