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REFERENCES 21. 1. Baserga, R., Estensen, R. D., Petersen, R. 0., and Layde, J. P. Inhibition of DNA Synthesis in Ehrlich Ascites Cells by Actinomycin D. I. Delayed Inhibition by Low Doses. Proc. Nati. Acad. Sei. U. S., 54: 745-751, 1965. Beckwith, J. R., Pardee, A. B., Austrian, R., and Jacob, F. Coordination of Synthesis of the Enzymes in the Pyrimidine Pathway of E. coli. J. Mol. Biol., 5: 618-634, 1962. Bennett, L. L., Jr., Smithers, D., and Ward, C. T. Inhibition of DNA Synthesis in Mammalian Cells by Actidione, Biochim. Biophys. Acta, 87: 60-69, 1964. Bennett, L. L., Jr., Ward, V. L., and Brockman, R. W. Inhibi tion of Protein Synthesis in vitro by Cycloheximide and Re lated Glutarimide Antibiotics. Biochim. Biophys. Acta, 103: 478-485, 1965. Berlin, C. M., and Schimke, R. T. Influence of Turnover Rate on the Responses of Enzymes to Cortisone. Mol. Pharmacol., 1: 149-156, 1965. Breitman, T. R. The Feedback Inhibition of Thymidine Kin ase. Biochim. Biophys. Acta, 67: 153-155, 1963. Bresnick, E. Early Changes in Pyrimidine Biosynthesis After Partial Hepatectomy. J. Biol. Chem., 240: 2550-2556, 1965. Bresnick, E., and Thompson, U. B. Properties of Deoxythymidine Kinase Partially Purified from Animal Tumors. J. Biol. Chem., 240: 3967-3974, 1965. Bcher, N. L. R. Regeneration of Mammalian Liver. Intern. Rev. Cytol., 15: 245-300, 1963. Colombo, B., Felicetti, L., and Baglioni, C. Inhibition of Pro tein Synthesis by Cycloheximide in Rabbit Reticulocytes. Biochem. Biophys. Res. Commun., 18: 389-395, 1965. Estensen, R. D., and Baserga, R. Puromycin-Induced Necrosis of Crypt Cells of the Small Intestine of Mouse. J. Cell Biol., 30: 13-22, 1966. Fausto, N., and Van Lancker, J. L. Molecular Mechanisms of Liver Regeneration. IV. Thymidylic Kinase and Deoxyribomicleic Acid Polymerase Activities in Normal and Regen erating Liver. J. Biol. Chem., iJfl: 1247-1255, 1965. Fleck, A., and Munro, H. N. Precision of Ultraviolet Absorp tion Measurements in the Schmidt-Thannhauser Procedure for Nucleic Acid Estimation. Biochim. Biophys. Acta, 55: 571-583, 1962. Guidice, G., and Novelli, G. D. Effect of Actinomycin D on the Synthesis of DNA Polymerase in Hepatectomized Rats. Biochem. Biophys. Res. Commun., le: 383-387, 1963. Higgins, G. M., and Anderson, R. M. Experimental Pathology of the Liver. Restoration of the Liver in the White Rat Follow ing Partial Surgical Removal. A. M. A. Arch. Pathol., 12: 186202, 1931. Iloltzer, R. L., Oda, A., and Chiga, M. Effect of Actinomycin D on Deoxycytidylate Deaminase Activity of Rat Liver After Partial Hepatectomy. Lab. Invest., 13: 1514-1519, 1964. Jacob, F., and Monod, J. Genetic-Regulatory Mechanisms in the Synthesis of Proteins. J. Mol. Biol., 3: 318-356, 1961. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. Protein Measurement with the Folin Phenol Reagent. J. Biol. Chem., 193: 265-275, 1951. Maley, G. F., Lorenson, M. G., and Maley, F. Inhibitors of Protein Synthesis: Effect on the Levels of Deoxycytidylate Deaminase, Thymidylate Synthetase and Thymidine Kinase in Regenerating Rat Liver. Biochem. Biophys. Res. Commun., 18: 364-370, 1965. Merits, I. Actinomycin Inhibition of RNA Synthesis in Rat Liver. Biochem. Biophys. Res. Commun., 10: 254-259, 1963. Noll, H., Staehelin, T., and Wettstein, F. O. Ribosomal Aggregates Engaged in Protein Synthesis: Ergosome Break down and Messenger Ribonucleic Acid Transport. Nature, 198: 632-638, 1963. Penman, S., Scherrer, K., Becker, Y., and Darnell, J. E. Polyribosomes in Normal and Polio Virus-Infected HeLa Cells and Their Relationship to Messenger RNA. Proc. Nati. Acad. Sei. U. S., 49: 654-662, 1963. Pilot, H. C., Peraino, C., Lmar, C., Jr., and Kennan, A. L. Template Stability of Some Enzymes in Rat Liver and Hepatoma. Proc. Nati. Acad. Sei. U. S., 5k 845-851, 1965. Reich, E. Biochemistry of Actinomycins. Cancer Res., 23: 1428-1441, 1963. Revel, M., and Hiatt, H. H. The Stability of Liver Messenger RNA. Proc. Nati. Acad. Sei. U. S., 51: 810-818, 1964. Roth, J. S. Increased Stability of Templates for Some Enzymes of DNA Synthesis in Tumors: Deoxycytidylate Deaminase, Thymidine and Thymidylate Kinase. Life Sci., 3: 1145-1149, 1964. Schwartz, H. S., Sodergren, J. E., Garofalo, M., and Sternberg, S. S. Actinomycin D Effects on Nucleic Acid and Protein Metabolism in Intact and Regenerating Liver of Rats. Cancer Res., 25: 307-317, 1965. Tomkins, G. M., Garren, L. D., Howell, R. R., and Peterkofsky, B. The Regulation of Enzyme Synthesis by Steroid Hormones: The Role of Translation. J. Cellular Comp. Physiol., 66 Suppl. 1 ; : 137-152, 1965. Trakatellis, A. C., Axelrod, A. E., and Montjar, M. Studies on Liver Messenger Ribonucleic Acid. J. Biol. Chem., 239: 42374244, 1964. Tsukada, K., and Lieberman, I. Liver Nuclear Ribonucleic CANCER RESEARCH VOL. 27.
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Milligan et al. [5] reported eight patients who initially were thought to have pulmonary tuberculosis because of the upperlobe distribution of their infiltrates. One case of apical P. carinll infection has been reported in a patient receiving prophylactic inhaled pentamidine [6]. During his first episode of P. carinil pneumonia, our patient had typical diffuse interstitial infiltrates. His second episode, which occurred while receiving prophylactic inhaled pentamidine treatments, was confined to the apices. The standard therapy for P. carinll pneumonia is either trimethoprim-sulfa or pentamidine. Both of these agents are effective, but they are frequently associated with toxicity [2]. Recently, inhaled pentamidine has been shown to be effective in the treatment of mild cases of P. carinii pneumonia [3]. This method of administration seems ideally suited for the treatment of P. carinll pneumonia because the organisms are.
In recent years, it has become evident that some apoenzymes of P4501 are closely associated with the synthesis of NO. In the liver, microsomes catalyze the oxidative denitration of NOHA, thus producing NO and citrulline, oxidation that is not inhibited by NO synthase inhibitors, but rather by classical P450 inhibitors, such as miconazole and troleandomycin 1 ; . NOHA is not the only substrate of rat liver microsomal P450 originating NO, because the reduction of pentamidine 2 ; or 18-nitro-oxyandrostenedione 3 ; also generate NO. In vascular tissues, the inhibition of the P450 of the carotid artery endothelium by inhaled anesthetics, clotrimazole, metyrapone, or SKF525A abolishes the NO-dependent relaxation induced by acetylcholine 4 ; . Formation of NO seems to be rather specific to isoforms of the CYP3A family 5 ; . Further supporting that P450 generates NO is the fact that cimetidine reduces in a dose-dependent manner the formation of NO induced by cytokines without affecting the mRNA of NO synthase 6 ; . The NO precursor, L-arginine, has been used clinically for a number of years as a vasodilator 7 ; in pathological conditions, such as angina pectoris, congestive heart failure, hypertensive emergencies, pulmonary hypertension, percutaneous angioplasty, and complications after cardiac catheterization 8 ; . On the other hand, NO synthase inhibitors, such as L-NAME, are considered as therapeutic agents in the treatment of endotoxemia and in the prevention of the hypotension associated with the treatment with cytokines 9.
| Pentamidine cream97-103 7 ; publisher: elsevier previous article next article view table of contents key: - free content - new content - subscribed content - free trial content keywords: imidazoline i 2 receptor ; pentamidine ; hypoglycemia ; pneumocystis carinii pneumonia language: english document type: research article doi: 1 1016 s0014-2999 98 ; 00386-0 affiliations: 1: department of pathology and laboratory medicine, university of north carolina at chapel hill, chapel hill, usa this article is hosted on another website.
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PMA ; , 3- 4, 5-dimethlythinzol-2-yl ; -2, 5-diphenyltetrazolium MTT ; , and pentamidine isethionate were supplied by Sigma. Parasites and cultures. A cloned line of L. infantum MHOM MA 67 ITMAP263 ; was used in all experiments. Axenically grown amastigote forms of L. infantum were maintained at 37C with 5% CO2 by weekly subpassages in a cell-free medium called MAA 20 medium for axenically grown amastigotes ; in 25-ml flasks, as previously described 34 ; . From a starting inoculum of 5 105 amastigotes ml, a cell density of about 5 107 parasites ml was obtained on day 7. MAA 20 consisted of modified medium 199 Gibco BRL ; with Hanks' balanced salts supplemented with 0.5% soya trypto-casein Pasteur Diagnostics, Marne la Coquette, France ; , 0.01 mM bathocuproine disulfonic acid, 3 mM L-cysteine, 15 mM D-glucose, 5 mM L-glutamine, 4 mM NaHCO3, 0.023 mM bovine hemin, 25 mM HEPES final pH, 6.5 ; , and 20% fetal calf serum FCS ; . Viability test. To estimate the 50% inhibitory concentration of drugs, the MTT micromethod was used as previously described 34 ; . Briefly, axenically grown amastigotes were seeded in a volume of 100 l in 96-well flat-bottom microtrays. Drugs were added, and after 72 h of incubation 10 l of MTT 10 mg ml ; was added to each well and plates were further incubated for 4 h. The reaction was then stopped by the addition of 100 l of 50% isopropanol10% sodium dodecyl sulfate. The plates were incubated for an additional 30 min under agitation before reading the optical density at 570 nm. DNA construct and transfection. The pSP LUC vector used in transienttransfection experiments was made by subcloning the intergenic region of the -tubulin gene 24 ; as an EcoRI-BamHI fragment into pSP72 Promega ; . The LUC gene was amplified by PCR and subcloned into the BamHI site of vector pSP filled in by Klenow polymerase to yield pSP LUC. The vector PGM NEO LUC has been described before 30 ; . Drug efficacy assay in THP-1. The growth of the luciferase-expressing amastigotes of L. infantum in a human leukemia monocyte cell line THP-1 cells ; was evaluated according to the method described by Gebre-Hiwot et al. 17 ; , with modifications. Briefly, THP-1 cells were cultured in RPMI 1640 medium supplemented with 10% FCS, 2 mM glutamine, 100 IU of penicillin ml, and 100 g of streptomycin ml. THP-1 cells in the log phase of growth were differentiated by incubation for 2 days in medium containing 20 ng of PMA ml Sigma ; , which induced differentiation and caused the cells to become adherent. THP-1 cells treated with PMA were washed with prewarmed medium and then infected with stationary-phase extracellular amastigotes in 96-microwell plates Nunc ; at a parasite macrophage ratio of 2: 1 for 2 h at 37C with 5% CO2. Noninternalized parasites were removed. Serial dilutions of each drug were made in the RPMI medium supplemented with 10% FCS and were dispensed in wells. After 5 days of drug exposure, wells containing adherent differentiated THP-1 cells were and pentasa.
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Petitively inhibits putrescine and spermidine uptakes in both strains, indicating a common carrier-mediated mechanism. In both strains, Km values for putrescine and spermidine as well as the Ki for pentamidine are higher in axenic amastigotes than in promastigotes.
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Somers DC, Dale AM, Seiffert AE, Tootell RBH 1999 ; Functional MRI reveals spatially specific attentional modulation in human primary visual cortex. Proc Natl Acad Sci USA 96: 16631668. Steinman RM, Haddad GM, Skavenski A A, Wyman D 1973 ; Miniature eye movement. Science 181: 810819. Steriade M, Domich L, Oakson G 1986 ; Reticularis thalami neurons revisited: activity changes during shifts in states of vigilance. J Neurosci 6: 6881. Thompson KG, Zhou Y, Leventhal AG 1994 ; Direction-sensitive X and Y cells within the A laminae of the cat's LGNd. Vis Neurosci 11: 927938. Tootell RB, Silverman MS, Switkes E, De Valois RL 1982 ; Deoxyglucose analysis of retinotopic organization in primate striate cortex. Science 218: 902904. Tootell RB, Silverman MS 1985 ; Two methods for f lat-mounting cortical tissue. J Neurosci Methods 15: 177190. Tootell RB, Hamilton SL, Silverman MS, Switkes E 1988a ; Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions. J Neurosci 8: 15001530. Tootell RB, Swikes E, Silverman MS, Hamilton SL 1988b ; Functional anatomy of macaque striate cortex. Retinotopic organization. J Neurosci 8: 15311568. Tootell RBH, Born RT, Hamilton SL 1988c ; Studies of primate visual cortex using a double-label DG technique and color autoradiography. Soc Neurosci Abstr 14: 897. Tootell RB, Hadjikhani N, Hall EK, Marrett S, Vanduffel W, Vaughan JT, Dale A M 1998 ; The retinotopy of visual spatial attention. Neuron 21: 14091422. Treisman AM, Gelade G 1980 ; A feature-integration theory of attention. Cogn Psychol 12: 97136. Treue S, Maunsell JH 1996 ; Attentional modulation of visual motion processing in cortical areas MT and MST. Nature 382: 539541. Tsotsos JK 1990 ; Analyzing vision at the complexity level. Behav Brain Sci 13: 423469. Tsotsos JK, Culhane S, Cutzu F 1999 ; From theortical foundations to a hierarchical circuit for selective attention. In : Visual attention and cortical circuits Braun J, Koch C, eds ; . Cambridge, MA: MIT Press in press ; . Van der Heijden A HC, Schreuder R, Wolters G 1985 ; Enhancing single-term recognition accuracy by cueing spatial locations in vision. Quart J Exp Psychol A37: 427434. Van der Heijden A HC, Wolters G, Enkeling M 1988 ; The effects of.
Chloroquine phosphate 250mg Tablet 150 mg as base ; Chloroquine phosphate inj 250mg 150mg as base ; 5ml, ; Ampoule Chloroquine phosphate 80mg 5ml Syrup Chlorquine phosphate 120mg equivalent to 75mg chloraquine base 5ml Syrup Diloxanide furoate 500mg Tablet Dehydroemetine Injection Emetine Hcl 60mg Injection Hydroxychloroquine 200mg sulphate Tablet Metronidazole 200mg Tablet Metronidazole 250mg Tablet Metronidazole 400mg Tablet Metronidazole 500mg Tablet Metronidazole 5mg ml, 100ml ; I.V. Infusion Metronidazole as benzoate 200mg 5ml, Suspension Metronidazole 500mg Suppository Meglumine antimonate inj equivalent to 85mg of pentavalent antimony per ml Nifuratel 200mg oral Tablet Nimorazole 250mg oral Tablet Primaquine as phosphate 15mg Tablet Pyrimethamine 25mg Tablet Pyrimethamine 25mg + sulphadoxine 500mg Tablet Pentamidine isethionate inj powder for inj 300mg vial Pentamidine isethionate nebuliser solution 300mg bottle Proguanil Hcl 100mg tab Sodium stibogluconate inj equivalent to pentavalant.antimony 100mg ml 6ml ; Vial Sodium stibogluconate inj equivalent to pentavalant.antimony 100mg ml 100ml ; Vial Spiramycin 1500000 IU equivalent to 468.75mg Tablet Spiramycin 1600000 IU equivalent to 500mg Tablet Spiramycin 3000000 IU Tablet Spiramycin Injection Tinidazole 500mg Tablet and pentostatin.
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The primary 3D review. Although it was not proven, a higher sensitivity of the primary 3D review compared to the primary 2D review for polyp detection was also suggested 1 ; . A primary 3D review, on the other hand, has some disadvantages. The primary 3D review is less time-efficient than the 2D review 46 49 ; , and it may not work well with a protocol of reduced preparation and fecal tagging that leaves a large amount of fecal residue in the colon Fig. 5 ; . Although a 3D fly-through may be capable of detecting all polyp-like structures in a colon, in cases of excess luminal protrusions, differentiation of a true polyp from polyp-like stool by repeated reference to the 2D images or to a translucency map based on lesion density would render the interpretation exhausting. Moreover, those lesions buried under fecal material would not be detectable at all during the 3D fly-through. Unless robust electronic cleansing is available i.e. digital subtraction of the tagged feces and fluid ; 50, 51 ; with the capability of removing the majority of pseudopolyps i.e. feces ; before the 3D review, primary 3D review of CTC that's performed with reduced preparation, and especially laxative-free CTC, is not likely to be feasible. In contrast, the 2D interpretation of tagged cases is still effective without digital subtraction Fig. 5B ; . There is not any one correct method for performing interpretation of CTC. Almost all cases will require a combination of both the 3D and 2D review methods. Therefore, readers should be well-versed with both methods.
Several secondary structure programs predicted three large ot-helical regions in the carboxyl terminus and one highly hydrophobic helical region in the center of the polypeptide residues 196 to 222 ; which appears to be a potential membrane-associated helix. However, the overall secondary structure lacks the multiple transmembrane domains of typical membrane transport proteins. The sequence of the amino terminus does not resemble typical mitochondrial import or secretory signal sequences, although such sequences are not always clearly distinct or located in the amino terminus. The polypeptide contains five Cys residues in the carboxyl-terminal half of the polypeptide, suggesting the possibility of a Cterminal domain stabilized by disulfide bonds. Nevertheless, we are not able to infer from the sequence either a cellular location or a biochemical function for Pntlp. Role of PNTI gene in resistance to pentamidine and other inhibitors. The PNTI gene affected the inhibition of growth and the induction of petite mutants by pentamidine, but it did not significantly affect the inhibition of respiration by pentamidine. This is consistent with the hypothesis that the primary inhibitory effect of pentamidine is not the inhibition of respiration 15 ; . The overexpression or disruption of PNTI had no effect on the toxicities of a wide variety of drugs including inhibitors of respiration, mitochondrial and cytoplasmic protein synthesis, or topoisomerase II ; . PNT1 is therefore not a typical pleiotropic drug resistance gene of S. cerevisiae. Although chromosome XVR contains a cluster of PDR genes between ADE2 and HIS3, this region is distinct from the PNT1 locus and the sequence of PNT1 is distinct from those of known PDR genes. The overexpression of PNT1 induced slight cross-resistance to other positively charged, DNA-interacting compounds Berenil, ethidium bromide ; . Although cross-resistance was much lower than the resistance to pentamidine 2versus 10-fold ; , the mechanisms of resistance may be similar. Implications for pentamidine mechanism of action and pentamidine therapy. Because the insertion of TRP1 within the PNT1 gene did not inhibit growth, the primary growth-inhibitory effect of pentamidine in S. cerevisiae cannot be inactivation of the PNTI gene product. Nevertheless, both growth inhibition and petite mutant induction were affected by PNT1 expression, so we infer that PNT1 affects a general process involved in pentamidine toxicity, such as enhanced drug efflux, increased detoxification, or increased target number. Other molecular approaches such as immunolocalization of Pntlp ; will now allow the identification of the organelles and other cellular components involved in pentamidine toxicity and metabolism. The characterization of the PNTI gene begins a molecular description of these components and the mechanisms of resistance to pentamidine in fungi and peppermint.
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5 data derived from crystallization studies and experimental details regarding the type of glycosylation, this information will aid in confirmation of previous findings, e.g. proteinglycan interaction studies. The presence of modification sites on interaction surfaces may reveal completely new features in this context. For elucidation of N-glycosylation sites a very convenient method is present using the properties of PNGaseF[7]. This enzyme not only cleaves all types of N-glycans with few exceptions[8] from the polypeptide backbone but possess also additional amidase activity during this process. Therefore, PNGaseF converts asparagine to aspartic acid during the cleavage reaction. This results in a 1 mass shift detectable by most of the recently.
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