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Biomedical subjects

B L Lee

Publications and source records attributed to B L Lee.

At least 145 records · Page 8Linked to original sources
PubMed1988

Interaction of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with synthetic DNA containing a promoter for T7 RNA polymerase.

The interaction of 4'-N(2-aminoethyl)aminomethyl-4,5',8-trimethylpsoralen-modified oligonucleoside methylphosphonates with synthetic ds-DNA containing a T7 RNA polymerase promoter was studied. The oligomers effectively crosslinked with either coding or noncoding ss-DNA when irradiated at 365 nm, but not with ds-DNA. The extent of the crosslinking reaction, which was complete within 16 min: (a) reached its maximum at an oligomer concentration of 3 microM; (b) remained constant below the Tm of the duplex and then rapidly decreased; and (c) appeared to depend upon the sequence surrounding the psoralen crosslinking site. An oligomer crosslinked to the template strand inhibited transcription by T7 RNA polymerase whereas an oligomer crosslinked to the non-template strand had only a small inhibitory effect. Oligomers did not crosslink to ds-DNA undergoing transcription nor did they inhibit the transcription reaction.

Base Sequence↗
PubMed1988

Interaction of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with single-stranded DNA.

Oligodeoxyribonucleoside methylphosphonates derivatized at the 5' end with 4'-(amino-alkyl)-4,5',8-trimethylpsoralen were prepared. The interaction of these psoralen-derivatized methylphosphonate oligomers with synthetic single-stranded DNAs 35 nucleotides in length was studied. Irradiation of a solution containing the 35-mer and its complementary methylphosphonate oligomer at 365 nm gave a cross-linked duplex produced by cycloaddition between the psoralen pyrone ring of the derivatized methylphosphonate oligomer and a thymine base of the DNA. Photoadduct formation could be reversed by irradiation at 254 nm. The rate and extent of cross-linking were dependent upon the length of the aminoalkyl linker between the trimethylpsoralen group and the 5' end of the methylphosphonate oligomer. Methylphosphonate oligomers derivatized with 4'-[[N-(2-aminoethyl)amino]methyl]- 4,5',8-trimethylpsoralen gave between 70% and 85% cross-linked product when irradiated for 20 min at 4 degrees C. Further irradiation did not increase cross-linking, and preirradiation of the psoralen-derivatized methylphosphonate oligomer at 365 nm reduced or prevented cross-linking. These results suggest that the methylphosphonate oligomers undergo both cross-linking and deactivation reactions when irradiated at 365 nm. The extent of cross-linking increased up to 10 microM oligomer concentration and dramatically decreased at temperatures above the estimated Tm of the methylphosphonate oligomer-DNA duplex. The cross-linking reaction was dependent upon the fidelity of base-pairing interactions between the methylphosphonate oligomers and the single-stranded DNA. Noncomplementary oligomers did not cross-link, and the extent of cross-linking of oligomers containing varying numbers of noncomplementary bases was greatly diminished or eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1988

Hybrid hexanucleotide duplex containing cyclonucleotides and deoxynucleotides: the d(TA) segment can adopt a high anti left-handed double-helical structure.

It is known that oligonucleotides containing cyclonucleosides with a high anti (intermediate between anti and syn) glycosidic conformation adopt left-handed, single- and double-helical structures [Uesugi, S., Yano, J., Yano, E., & Ikehara, M. (1977) J. Am. Chem. Soc. 99, 2313-2323]. In order to see whether DNA can adopt the high anti left-handed double-helical structure or not, a self-complementary hexanucleotide containing 6,2'-O-cyclocytidine (C(o)), 8,2'-O-cycloguanosine (G(o)), thymidine, and deoxyadenosine, C(o)G(o)dTdAC(o)G(o), was synthesized. Imino proton NMR spectra and the results of nuclear Overhauser effect experiments strongly suggest that C(o)G(o)dTdAC(o)G(o) adopts a left-handed double-helical structure where the deoxynucleoside residues are involved in hydrogen bonding and take a high anti glycosidic conformation. A conformational model of the left-handed duplex was obtained by calculation with energy minimization. Thus it appears that DNA can form a high anti, left-handed double helix under some constrained conditions, which is quite different from that of Z-DNA.

DNA↗
PubMed1988

Anticoccidial evaluation of halofuginone, lasalocid, maduramicin, monensin and salinomycin.

The activities of five anticoccidials were compared against Eimeria species in/of chickens, in controlled in vivo and in vitro laboratory studies. Two more recent and potent market entries (maduramicin and halofuginone) were compared with three older polyether antibiotic anticoccidials (monensin, lasalocid and salinomycin). Halofuginone, lasalocid, maduramicin, monensin and salinomycin were evaluated at 3, 125, 5, 120 and 66 ppm, respectively, of active drug in the diets. At these levels, all five drugs demonstrated significant activity against Eimeria tenella, E. maxima, E. necatrix, E. brunetti and E. acervulina (in vivo). Monensin was least effective against E. tenella, and one of the lesser efficacious drugs against E. necatrix, maduramicin, was least effective against E. maxima. In studies of single Eimeria species infections, comparable weight gains were noted for the drugs. In the mixed Eimeria species infections, however, birds treated with maduramicin had significantly higher weight gains than did birds medicated with monensin. Unlike in vivo potencies, titration in vitro indicated that monensin was most potent (active at 10(-6) mcg ml-1), and maduramicin and lasalocid least potent (inactive at less than or equal to 10(-3) mcg ml-1).

Animals↗
PubMed1987

Effects of PGE1 or PGE2 and/or acetazolamide on expulsion of Nippostrongylus brasiliensis from rats.

PGE1 and PGE2 have been reported to enhance natural expulsion of Nippostrongylus brasiliensis, a nematode parasite, from the intestine of the rat. Mucus production may also be a key element of worm rejection. Our study attempts to determine if 1) PGE1 or PGE2 alter the normal course of infection with N. brasiliensis in rats, 2) a known mucous enhancing drug, acetazolamide, can augment the rate of worm expulsion, and 3) combinations of prostaglandins and acetazolamide affect N. brasiliensis in the rat. Rats were inoculated with approximately 1,000 infective larvae of N. brasiliensis. Animals were administered, intraduodenally, one of the following: 0.2 ml 0.9% NaCl; 0.2 ml 100% ethanol; 250 micrograms PGE1/0.2 ml 100% ethanol; 250 micrograms PGE2/0.2 ml 100% ethanol; 250 micrograms acetazolamide/0.2 ml 100% ethanol; 250 micrograms PGE1 or PGE2 + 250 micrograms acetazolamide/0.2 ml 100% ethanol. These solutions were given in a single bolus on day 6 postinoculation (PI) or twice daily on days 6-9 PI. Following these treatments the number of parasite ova per gram feces per day for days 6-10 PI and numbers of worms present at necropsy on day 10 PI were determined. Treatment with prostaglandins or acetazolamide or both failed to adversely affect egg deposition by adult female worms or the number of worms in the small intestine. These results do not support the involvement of prostaglandins in the expulsion of N. brasiliensis from the host intestine.

Acetazolamide↗
PubMed1987

Detecting in vitro anthelmintic effects with a micromotility meter.

An in vitro target parasite anthelmintic assay utilizing a micromotility meter has been developed and validated. Haemonchus contortus, an economically important ruminant helminth with worldwide distribution, was the parasite used in the model. Four commercially available ruminant anthelmintics (albendazole, ivermectin, levamisole hydrochloride and coumaphos) were initially evaluated at concentrations of 200, 150, 100 and 50 micrograms ml-1. All four significantly affected helminth motor activity and were active at 200 and 150 micrograms ml-1, and three of the four were active at 100 and 50 micrograms ml-1. An Upjohn compound (p-toluoyl chloride phenylhydrazone) was also assayed and was significantly active at all four levels. In a subsequent titration study, albendazole, levamisole hydrochloride, ivermectin and the hydrazone were significantly active at 100 and 10 micrograms ml-1; only levamisole hydrochloride and the hydrazone were active at 1.0 microgram ml-1. None of the drugs were active at 0.1 microgram ml-1. The data indicate that the in vitro H. contortus assay utilizing the micromotility meter is sensitive, accurate, rapid, repeatable, and inexpensive. With additional effort, this model can be extended to incorporate other target helminth parasites and stages of development. This in vitro assay system should be a valuable addition to the battery of tests used to identify anthelmintic candidates, monitor drug resistance, and define the kinetics and mode of action of drugs.

Albendazole↗
PubMed1987

Prolonged absorption with development of tolerance to toxic effects after cutaneous exposure to nicotine.

This report describes a patient who developed nicotine poisoning after cutaneous application of nicotine sulfate. Measurement of nicotine and metabolite levels in the blood demonstrated prolonged absorption of nicotine despite vigorous skin decontamination. This suggests that the skin may be a reservoir for slow release of nicotine into the circulation. Despite extraordinarily high levels of nicotine, the patient had full resolution of signs and symptoms of intoxication, indicating rapid and profound development of tolerance.

Administration, Topical↗
PubMed1987

Influence of tobacco abstinence on the disposition kinetics and effects of nicotine.

Habitual tobacco smoking accelerates the metabolism of many drugs. With tobacco abstinence, it was expected that nicotine metabolism would be slower than when smoking. To test this hypothesis, the disposition kinetics of intravenous nicotine were studied in 20 healthy smokers while smoking, after abstaining from smoking for 1 week, and (in six subjects) when smoking again. Cardiovascular responses to nicotine were also measured. Unexpectedly, total and nonrenal clearance of nicotine increased by 36% and 39%, respectively, during abstinence. The increase in clearance after brief abstinence suggests that nicotine or its metabolites or another component of cigarette smoke inhibits nicotine metabolism in smokers. Cardiovascular responses to nicotine were greater after 1 week compared with overnight abstinence, consistent with loss of tolerance.

Adult↗
PubMed1987

Cigarette abstinence, nicotine gum, and theophylline disposition.

When cigarette smokers with chronic lung disease become acutely ill or require surgery, they are often forced to stop smoking and may use nicotine gum. Smoking is known to accelerate the metabolism of theophylline, but the effects of short-term abstinence or nicotine gum on theophylline metabolism have not been reported. We studied the effects of brief tobacco abstinence and nicotine gum on theophylline elimination in healthy volunteers. Abstinence from smoking for 1 week resulted in a 37.6% decrease in clearance and a 35.8% increase in half-life. Nicotine gum had no effect on theophylline clearance. Our data indicate that at least partial normalization of the enzyme-inducing effects of smoking can be seen after brief cigarette abstinence. For smokers who are taking theophylline chronically, their dose of theophylline will need to be reduced by one fourth to one third after brief tobacco abstinence. Plasma concentration monitoring may be necessary for optimal dosing of theophylline in such patients.

Adult↗
PubMed1987

Anticoccidial activity of alborixin.

Alborixin, a polyether antibiotic with ionophore properties, was evaluated to determine the effect of the drug on weight gain of chickens and to define the anticoccidial spectrum of activity. The 50-ppm concentration in the diet was identified as the maximum level that did not significantly reduce weight gain beyond that of monensin (standard drug); consequently, the drug was evaluated for anticoccidial activity at this dilution. At the 50-ppm level, alborixin demonstrated broad-spectrum anticoccidial activity; however, the drug lacked Eimeria necatrix efficacy. Monensin and maduramycin were significantly more efficacious than alborixin as a treatment for several species of Eimeria. Higher concentrations of alborixin (greater than 50 ppm) appear essential to achieve broad-spectrum and comparable anticoccidial activity, however, these levels substantially depressed weight gains. Alborixin is similar to many other polyethers in that weight gains are adversely affected at drug levels essential for solid broad-spectrum anticoccidial activity.

Animals↗
PubMed1986

Precluding coccidiosis with an anti-coprophagia drug.

Floor-pen studies were conducted to ascertain whether coccidiosis could be prevented by using a drug added to the litter to preclude coprophagia and ingestion of infective oocysts. An experimental drug (1-pyrrolidinebutyramide, 2-methyl-alpha,alpha-diphenyl) was added to litter contaminated with sporulated Eimeria tenella oocysts. Thereafter 7-day-old broiler chicks were reared on the litter for a nine-day period. Mortality, lesion scores and dropping scores were the criteria selected to determine efficacy. Treatment of the litter at the lowest level (2.3 g kg-1) did not reduce the incidence or severity of the disease, whereas treatment at two higher levels (11.5 and 23.0 g kg-1) significantly reduced both (incidence and severity). The highest level was the most efficacious; however, drug toxicity was also encountered at this level.

Animals↗