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991.
Haemodynamic effects of intravenous indoramin (5-20 mg) were measured in ten healthy volunteers. Slight falls in arterial and central venous blood pressures were noted but no significant changes in heart rate, right atrial pressure, cardiac output or derived values occurred, except for a fall in peripheral vascular resistance in three cases. An increase in skin blood flow to the feet was observed. An attempt was made to determine the mechanisms of these responses and it was concluded that the drug was an alpha adrenoceptor blocking agent which appeared to act preferentially on those receptors controlling blood flow to the skin of extremities. 相似文献
992.
Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine). 下载免费PDF全文
M B Coleman Z H Lu C M Smith nd J G Adams rd A Harrell M Plonczynski M H Steinberg 《The Journal of clinical investigation》1995,95(2):503-509
We studied the molecular basis of transfusion-dependent hemolytic anemia in an infant who rapidly developed the phenotype of beta thalassemia major. DNA sequence of one beta-globin gene of the proband revealed two mutations, one for the moderately unstable hemoglobin (Hb) Köln and another for a novel codon 32 cytosine-thymidine-guanine-->cytosine-adenine-guanine transversion encoding a leucine-->glutamine mutation. A hydrophilic glutamine residue at beta 32 has an uncharged polar side chain that could potentially distort the B helix and provoke further molecular instability. This new hemoglobin was called Hb Medicine Lake. Biosynthesis studies showed a deficit of beta-globin synthesis with early loss of beta-globin chains. An abnormal unstable hemoglobin, globin chain, or tryptic globin peptide was not present, demonstrating the extreme lability of this novel globin. Hb Medicine Lake mRNA was present, but an aberrantly spliced message was not. Absence of an abnormal beta-globin gene in the mother makes it likely that a de novo mutation occurred in the proband. The molecular pathogenesis of Hb Medicine Lake illustrates a mechanism whereby the phenotype of a genetic disorder, like the mild hemolytic anemia associated with a hemoglobinopathy, can be modulated by a coincident mutation in the same gene. 相似文献
993.
Candida dubliniensis is a recently described Candida species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected patients and patients with AIDS. The majority of C. dubliniensis clinical isolates tested to date are susceptible to the commonly used antifungal drugs, including fluconazole, ketoconazole, itraconazole, and amphotericin B. However, the appearance of fluconazole-resistant C. dubliniensis strains in this patient group is increasing. Histatins are a family of basic histidine-rich proteins present in human saliva which have therapeutic potential in the treatment of oral candidiasis. The mechanism of action of histatin is distinct from that of commonly used azole and polyene drugs. Characterization of the antifungal activity of histatin has mainly been carried out using C. albicans but it is also effective in killing C. glabrata and C. krusei. Here we report that C. dubliniensis is also susceptible to killing by histatin 3. The concentration of histatin 3 giving 50% killing (the IC(50) value) ranged from 0.043 to 0.196 mg/ml among different strains of C. dubliniensis. The least-susceptible C. dubliniensis strain, P9224, was found to internalize histatin at a lower rate than the C. albicans reference strain CA132A. The dissociation constant (K(d)) for the least-susceptible strain (C. dubliniensis 9224) was ninefold higher than that for the C. albicans reference strain. These results suggest that histatin 3 may have potential as an effective antifungal agent, particularly in the treatment of oral candidiasis in HIV-infected patients and patients with AIDS in which resistance to the commonly used antifungal drug fluconazole has emerged. 相似文献
994.
995.
R I Hall J P Grant L H Ross R A Coleman M G Bozovic S H Quarfordt 《The Journal of clinical investigation》1984,74(5):1658-1668
Hepatic steatosis frequently complicates total parenteral nutrition (TPN). Some of the mechanisms responsible were examined in rats receiving calories as dextrose (CHO-TPN) or dextrose plus lipid emulsion (Lipid-TPN). Hepatic triglyceride content increased approximately threefold after CHO-TPN and twofold after Lipid-TPN (P less than 0.02). Hepatic triglyceride fatty acid composition reflected endogenous synthesis. Hepatic acetyl-Coenzyme A carboxylase specific activity increased fourfold after CHO-TPN and twofold after Lipid-TPN, and it correlated positively with hepatic lipid content (r = 0.82). The activities of the microsomal enzymes of complex lipid synthesis were unchanged in the TPN groups. Both TPN regimens suppressed hepatic triglyceride secretion, measured by the rise in plasma triglyceride and the incorporation of [14C]palmitic acid into plasma triglyceride after intravenous Triton. Hepatic triglyceride secretion correlated negatively with total hepatic lipid content (r = -0.89). CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both. Both adipose and cardiac lipase were higher for Lipid-TPN animals than for CHO-TPN or control animals. Hepatic 14C-triglyceride content was increased in both TPN groups as compared with controls after the injection of 1-[14C]-palmitic acid. This increment was proportional to the decreased hepatic secretion. Triglyceride fatty acid oxidation was significantly suppressed by CHO-TPN, less so by Lipid-TPN. Free fatty acid oxidation was suppressed only by CHO-TPN. The results suggest that the steatosis induced by TPN in rats was due to enhanced hepatic synthesis of fatty acid and reduced triglyceride secretion. Reduced hepatic triglyceride uptake, enhanced fatty acid oxidation, and enhanced peripheral tissue plasma triglyceride lipolysis when CHO-TPN is supplemented with lipid may modulate the accumulation of hepatic triglyceride and, along with reduced synthesis of fatty acid, lead to a lower hepatic triglyceride content. 相似文献
996.
Pratt LH Coleman RA 《Proceedings of the National Academy of Sciences of the United States of America》1971,68(10):2431-2435
An immunocytochemical assay, which localizes phytochrome in situ, indicates that this plant chromoprotein is associated with both nuclei and plastids, in addition to the cytoplasm. In an etiolated oat shoot, phytochrome is most abundant just behind the apex of the coleoptile, where it is associated with parenchyma cells; it is apparently absent at the extreme apx of the coleoptile. Further back from the tip, phytochrome is found in the epidermal cells of the coleoptile; it decreases in concentration toward the node, where it is again abundant. Phytochrome is also abundant in the extreme apical cells of young adventitious roots and in association with the procambium of the mesocotyl. 相似文献
997.
Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A-chain immunotoxin 总被引:1,自引:0,他引:1
The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo. 相似文献
998.
J M Clark R V Coleman 《Proceedings of the National Academy of Sciences of the United States of America》1976,73(5):1598-1602
Inelastic electron tunneling spectra of nucleosides and nucleotides are presented which show that detailed information on the vibrational spectra of these molecules can be obtained from a few micrograms of material. A series of studies on adenine derivatives demonstrates that unambiguous identification of a large number of slightly different derivatives can be carried out by means of this technique. 相似文献
999.
Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection 下载免费PDF全文
Coleman FT Mueschenborn S Meluleni G Ray C Carey VJ Vargas SO Cannon CL Ausubel FM Pier GB 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(4):1949-1954
No transgenic cystic fibrosis (CF) mouse model developed to date mimics the major clinical phenotype found in humans with CF, chronic Pseudomonas aeruginosa lung infection. In a transgenic CF transmembrane conductance regulator (cftr) mouse colony, we found WT, heterozygous, and homozygous CF mice housed in the same cage became chronically colonized in the oropharynx with environmental P. aeruginosa when the bacterium was present in drinking water. Elimination of P. aeruginosa from drinking water resulted in clearance in most WT and CF heterozygous, but not homozygous mice. For experimental evaluation, a combination of specific animal husbandry techniques and an oral infection route showed cftr(-/-) mice but not WT mice can be chronically colonized by P. aeruginosa with subsequent lung translocation, yielding a pathologic picture indicative of chronic lung infection. In some instances, mucoid isolates of P. aeruginosa were recovered from lungs, indicating conditions were present for conversion to mucoidy. Overexpression of human CFTR in the lungs of WT mice markedly accelerated the clearance rate of P. aeruginosa, demonstrating that lung levels of CFTR play an important role in defense against infection. P. aeruginosa mutants unable to express the surface polysaccharide alginate or the global regulator GacA were deficient in their ability to colonize the mice. CF mice made potent immune responses to P. aeruginosa outer membrane antigens. Overall, we found that under the proper conditions, transgenic CF mice are hypersusceptible to P. aeruginosa colonization and infection and can be used for evaluations of lung pathophysiology, bacterial virulence, and development of therapies aimed at treating CF lung disease. 相似文献
1000.
Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes 总被引:7,自引:1,他引:7
Cramer EM; Debili N; Martin JF; Gladwin AM; Breton-Gorius J; Harrison P; Savidge GF; Vainchenker W 《Blood》1989,73(5):1123-1129
The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source. 相似文献