Showing papers by "Eli Lilly and Company published in 1969"

In Vitro Antiviral Activity of Mycophenolic Acid and Its Reversal by Guanine-Type Compounds

Abstract: With the agar diffusion test and BS-C-1 cells, mycophenolic acid was found to give a straight-line dose-response activity in inhibiting the cytopathic effects of vaccinia, herpes simplex, and measles viruses. Plaque tests have shown 100% reduction of virus plaques by mycophenolic acid over drug ranges of 10 to 50 μg/ml and virus input as high as 6,000 plaque-forming units (PFU) per flask. Back titration studies with measles virus inhibited by mycophenolic acid have indicated that extracellular virus titers were reduced by approximately 3 logs10 and total virus was reduced by 1 log10. The agar diffusion test system lends itself readily to drug reversal studies. Mycophenolic acid incorporated into agar at 10 μg/ml gave 100% protection to virus-infected cells. Filter paper discs impregnated with selected chemical agents at concentrations of 1,000 μg/ml (20 μg per filter paper disc) were placed on the agar surface. Reversal of the antiviral activity of mycophenolic acid was indicated by virus breakthrough in those cells in close proximity to the filter paper disc. Chemicals showing the best reversal of the antiviral activity of mycophenolic acid were guanine, guanosine, guanylic acid, deoxyguanylic acid, and 2,6-diaminopurine. The reversal of antiviral activity was confirmed by titrations of virus produced with various amounts of both mycophenolic acid and guanine present and by isotope tracer methods with uptakes of labeled uridine, guanine, leucine, and thymidine in treated and nontreated, infected and noninfected cells as parameters. All antiviral effects of mycophenolic acid at 10 μg/ml could be reversed to the range shown by untreated controls by the addition of 10 μg/ml of those chemicals exhibiting reversal activity. Images

Substituted phenylalkanoic acids and derivatives thereof

Abstract: NOVEL ALKANOIC ACIDS, SUBSTITUTED BY 3-PHENOXYPHENYL OR 3-PHENYLTHIOPHENYL GROUPS, AND THE ESTERS, AMIDES, AMINES, ALCOHOLS, ETHERS, TETRAZOLES, CARBAMATES, AND UREAS RELATED THERETO AS WELL AS NOVEL INTERMEDIATES USEFUL IN THE PREPARATION OF SUCH COMPOUNDS. THE COMPOUNDS OF THIS INVENTION ARE USEFUL AS ANTIINFLAMMATORY, ANALGESIC, AND ANTIPYRETIC AGENTS.

Measurement of epithelial electrical characteristics with an automatic voltage clamp device with compensation for solution resistance

Abstract: A device is described which provides continuous measurement of transepithelial currents in isolated intestine or other tissues while clamping the transmural potential difference at zero or at a predetermined value. With tissues such as intestine, where the apparent tissue resistivity is of the same order as that of the bathing solution between the potential measuring electrodes and the tissue surface, compensation for the IR voltage drop in the solution is required. Using operational amplifiers and a special feedback circuit to drive a summing junction to virtual ground, the device enforces the equation E T ?E IR ?E VC =0 where ET is the measured transmural potetial difference between a pair of reversible electrodes and E IR is the potential drop in the solution due to the transmural currrent IT . The clamped voltage across the tissue E vc is thus equal to the true transmural potential difference. The circuit employed provides for readout of E T , E IR , E vc , and I T with uncertties emof 0.2 mV and 0.2 ?A and a 90 percent response time of 0.1 second. Because of its rapid automatic response, this devie is especially useful for accurately following transient changes in I T following temperature changes or the addition of transported solutes, metabolites, hormones, or drugs to the bathing medium.

Crystalline L-Asparaginase from Escherichia coli B

Abstract: L-Asparaginase has been crystallized from a partially purified extract of Escherichia coli B. The crystalline enzyme is homogeneous, as judged by analytical polyacrylamidegel electrophoresis and sedimentation behavior. This enzyme preparation is active in preventing lymphoma in mice and also has low glutaminase activity.

3 7-(ring-substituted) cephalosporin compounds

Abstract: CEPHALOSPORINS SUBSTITUTED IN THE 3-POSITION WITH A MERCAPTOTHIAZOLE OR MERCAPTOTETRAZOLE AND IN THE 7-POSITION WITH A PHENYL- OR THIENYLACETYL GROUP BEARING AN ALPHA AMINO OR HYDROXY GROUP ARE HIGHLY-ACTIVE ANTI BIOTICS YET ARE UNUSUALLY STABLE TOWARD CEPHALOSPORINASES AND METABLOIZING LIVER ENZYMES.

Cytokinin of Wheat Germ Transfer RNA: 6-(4-Hydroxy- 3-methyl-2-butenylamino)-2-methylthio-9-β-D-ribofuranosylpurine

Abstract: A new modified nucleoside is responsible, in part, for the cytokinin activity of transfer RNA from wheat germ. The structure as judged by mass spec-trometry is 6-(4-hydroxy-3-methyl-2-butenylamino)-2-methylthio-9-β-D-ribofuran-osylpurine. Unequivocal synthesis afforded material having ultraviolet, mass spectral, and chromatographic properties identical with those of the natural product.

A reevaluation of homothallism, heterothallism and the species concept in Sistotrema brinkmanni.

Abstract: SUMMARY The basidiomycete Sistotrema brinkmanni (Bres.) J. Erikss., as a nomenclatural entity, is a composite of homothallic, bipolar, and tetrapolar subspecies-all previously subjected to extensive cultural analysis by Biggs. Six further contributions to this system are discussed: (1) The marked enhancement of sporulation for the heterothallic as well as the homothallic subspecies on minimal media, (2) The detection of sporulation upon homokaryotic mycelia of heterothallic strains, an irregular feature recognized by Biggs in the bipolar Phlebia (Peniophora) luidoviciana (Burt) and by Raper and Krongelb in the tetrapolar Schizophyllum commune Fr., (3) The confirmation of homokaryotic dikaryosis as well as meiosis in homothallic strains of Sistotrema by the use of killing-kinetics and an analysis for recombination between auxotrophic mutations, (4) The demonstration, through nutritionally forced heterokaryosis and genetic recombination, that isolation between homothallic and bipolar counterparts of this system is not absolute, (5) The recognition of heterogenic incompatibility (recognized earlier by Biggs among "subgroups" of the tetrapolar subspecies) as common in all three subspecies, and (6) The induction of mutations (modifiers) that lead to self-sterility in homothallic strains and often disrupt homodikaryosis.

Automated system for performing sample measurements, dilutions and photometric measurements

Abstract: An automatic diluter and photometric reader adapted for use in the turbidimetric microbiological assays of antibiotics, vitamins, and the like, as well as in various other analytical assays.

A study of the behavior of propionyl erythromycin in blood by a new chromatographic method.

Abstract: By means of a two-step chromatographic technique propionyl erythromycin. and erythromycin can be separated from the normal blood components and then from each other. The relative amounts of each form of the antibiotic can be determined on bioautograph plates by comparison of the zone sizes with those of a set of reference standards. Using this method, we have found that when propionyl erythromycin is added to blood there is an initial rapid hydrolysis to erythromycin. The hydrolytic rate decreases markedly with time, however, and overall is much slower than in buffer solution at the same pH. The rate of hydrolysis in blood differs with different animal species.

An analysis of the lipolysis in vitro of obese-hyperglycaemic and diabetic mice.

Abstract: Mice homozygous for either the obese gene in linkage group XI or the diabetes gene in linkage VIII exhibit syndromes similar to those of diabetes mellitus in man, including obesity and hyperglycaemia A study of the lipolysis in vitro of the epididymal adipose tissue of 5 genotypes of mice, namely, ob/ob, ob/ob +, ob +/ob +, db/db, and db +/db +, demonstrates that the mutant homozygotes respond differently from wild type homozygotes to various lipolytic agents The agents tested were epinephrine, norepinephrine, isoproterenol, corticotropin 1–24, theophylline and N6, O2-dibutyryl-cyclic-adenosine3′,5′-monophosphate The response of ob/ob + tissue was the same as that of ob +/ob + tissue The data indicate that there is a defect with respect to lipolysis in ob/ob and db/db mice This is discussed in light of the involvement of cyclic AMP

Metabolism of D-cephaloglycin-14C and L-cephaloglycin-14C in the rat.

Abstract: The fate of the orally effective antibiotic D-cephaloglycin and its much less active L-enantiomer has been studied in the rat. D-Cephaloglycin-14C is metabolized by two pathways, (1) hydrolysis of the amide linkage to form D-2-phenylglycine-14C and (2) deacetylation to form deacetyl-D-cephaloglycin-14C. D-Cephaloglycin is absorbed from the gastro-intestinal tract at least in part as the intact antibiotic, L-Cephaloglycin-14C is rapidly metabolized to L-2-phenylglycine-14C and its metabolites. In contrast to the results with D-cephaloglycin-14C, no intact L-cephaloglycin-14C or deacetyl-L-cephaloglycin was excreted in the urine of rats.

Process for the crystallization of the ammonium and alkali metal salts in insulin

Abstract: WHILE RECOVERING 90-95 PERCENT OF THE INSULIN FROM AN AQUEOUS-ACID PANCREATIC EXTRACT. INSULIN IS ISOLATED AND PURIFIED FROM AN INSULIN-CONTAINING SOLUTION BY THE ADJUSTMENT OF THE BASICITY TO ABOUT PH 7.210.0 AND THE ALKALI METAL ION OR AMMONIUM ION CONCENTRATION TO ABOUT 0.2 M TO 1.0M, THEREBY CAUSING CRYSTALLIZATION OF THE ALKALI METAL OR AMMONIUM SALT OF INSULIN. THE METHOD UPGRADES INSULIN FROM ABOUT 2 INTERNATIONAL UNITS (I.U.) PER MILLIGRAM TO ABOUT 22-26 I.U. PER MILLIGRAM

Multilayer dispenser for pills

Abstract: The invention relates to a pill dispenser having a plurality of pill compartments arranged in layers. The layers are relatively rotatable on a common axis and are provided with multiple position clutch means for aligning the compartments of preceding layers on repeated advancement of the top layer relative to the bottom layer as the pills are dispensed in sequence.

The relationship between critical oxygen level and antibiotic synthesis of capreomycin and cephalosporin C

Abstract: This paper illustrates the type of conclusions which may be reached by the use of an electrode for measuring oxygen tension in fermentation broths. The critical oxygen level, based on oxygen uptake, and the minimum oxygen tension necessary for maximum antibiotic synthesis for two commercial antibiotic fermentations, capreomycin and cephalosporin C, were studied. Capreomycin yields were depressed at an oxygen tension which was slightly below the critical oxygen level. Cephalosporin C synthesis was depressed at an oxygen tension higher than the critical oxygen level.

Hydroxyesters of hexa- and octahydroindoloquinolines

Abstract: ESTERS OF LYSERGIC AND DIHYDROLYSERGIC ACIDS, INCLUDING 4-ALKYL, 4-ALKENYL AND 4-ARALKYL DERIVITIVES THEREOF, IN WHICH THE ESTERIFYING GROUP IS DERIVED FROM A DIHYDROXY OR TRIHYDROXY ALKYL ALCOHOL HAVING FROM TWO TO EIGHT CARBON ATOMS OR A C5 TO C11 CYCLOALKYL DIHYDOXY ALCOHOL, HAVING FROM 5 TO 8 RING CARBON ATOMS, THE ESTERS HAVING NEUROSEDATIVE ACTIVITY IN ANIMALS.

Functional Significance of the Sympathetic Nervous System in Production of Hypertension

Abstract: SEVERAL studies have implicated the sympathetic nervous system in the induction and maintenance of hypertension1–6. Other reports7,8 have shown that hypertension can be produced even after destruction of the sympathetic nervous system by immunosympathectomy. Treatment with anti-nerve growth factor9 results in a sub-total sympathectomy which is irreversible. Dahl has developed a method of accelerating production of salt hypertension by using L-triiodothyronine (T3) (ref. 10). Using this technique for producing hypertension, we have evaluated the functional significance of the sympathetic nervous system during induction of T3 and NaCl hypertension.

Extended Production of Insulin by Isolated Rabbit Pancreatic Islets; Evidence for Biosynthesis of Insulin:

Abstract: SummaryMethods for prolonged primary suspension cultures of rabbit pancreatic islets were established, and incorporation of carbon-14 labeled amino acids into insulin and other proteins was demonstrated.

Feeding and rectifying apparatus and method

Abstract: This disclosure is directed to a feeding and rectifying method and apparatus for orienting articles of manufacture in a predetermined manner onto a moving conveyor means. The feeding and rectifying apparatus comprises essentially a system of maintaining a supply of articles in a hopper through which the articles are randomly discharged. The dispensing of the articles from the hopper is attained by effecting relative rotation between the discharge means and the hopper, and orientation or rectification of the articles thus removed is effected by cooperating camming means and gauging means mounted for relative rotation with respect to one another operating on the article.

Synthesis of an antibiotic closely resembling fusidic acid by imperfect and perfect dermatophytes

Abstract: The antibiotic fusidic acid (Fusidin) was first found to be produced by the imperfect fungus Fusidium coccineum (Tubaki) reported by Godtfredsen et al.l) Recently, Nicot reported that fusidic acid was produced by Faecilomyces fusidioides2). This antibiotic was shown to be an acidic steroid3) which was biogenetically and structurally related to helvolic acid and cephalosporin Px4). Fusidic acid, characterized by low toxicity and oral activity, was shown to be clinically effective against penicillin-resistant staphylococci5) and appeared to be synergistic with benzylpenicillin against strains of Staphylococcus aureus in vivo and in vitroe). Several years ago a program was initiated in our laboratories to screen dermatophytes for the synthesis of cephalosporin or cephalosporin-like antibiotics. The dermatophytes studied were obtained from the Communicable Disease Center, Atlanta, Georgia and Columbia University Medical School.

Molecular orbitals for components of adenosine triphosphate

Abstract: Energies and charge distribution properties are obtained for ortho-, pyro-, and tri-phosphoric acids, and for adenine, D-ribose, adenosine, and adenosine-5′-monophosphate (AM P). Results are based upon a molecular orbital method in which all electrons are included and in which the Hamiltonian matrix elements are approximated by reference to exact SCF matrix elements for the model compounds, PO, HCOOH, C2H4, C2H6, and hypothetical H2CNH. Conclusions are in agreement with extended Huckel results on the charge distribution in the pyrophosphate bonds and on the participation of P 3d orbitals in the hybridization at P.

Determination of Pyrrolnitrin and Derivatives by Gas-Liquid Chromatography

Abstract: A gas-liquid chromatographic technique was applied to the separation of pyrrolnitrin and its derivatives. The simultaneous use of a flame detector and an electron capture detector made possible the distinction between the nitro derivatives of pyrrolnitrin and the other metabolites. The metabolites could be readily quantitated with the electron capture detector, offering a much more sensitive assay than the flame detector.