Abstract: Iodinatable bile salt derivatives are obtained by providing bile salts and their glycine and taurine conjugates with iodinatable groups. The radioiodinated compounds are useful in the radioimmunoassay of bile salts and in physiological studies. The preferred compound is cholylglycylhistamine. The synthesis of radioiodinated conjugates and their purification by extraction and silica gel chromatography are described.

Abstract: Certain trisubstituted pyrrolopyrimidine nucleosides are prepared from toyocamycin and have shown antitumor activity against L1210 and P388 murine leukemia. The particular compounds of interest are selected from the following structural formula: ##STR1## where X is haloY is halo; --NH.sub.2 ; --SH, --SR (where R is lower alkyl, benzyl); --OR (where OR is methoxy or alkoxy or where alk is C1-C6); amino (where the amino is --NH.sub.2, -alkyl amino or -dialkyl amino and alkyl is C1-C6); gamma gamma dimethyl allyl amino; benzyl amino; phenyl amino; selenoZ is CN; CXNH.sub.2 where X is .dbd.0, .dbd.S, or .dbd.Se, .dbd.NH, .dbd.NHNH.sub.2, .dbd.NOH. OR Z is = --CH.sub.2 NH.sub.2, --COR.dbd.NHRib.dbd..beta.-D-ribofuranosylPreferred members of this group of compounds are shown by the following structural formula: ##STR2## where X is ClY is Cl or NH.sub.2Z is CN, CONH.sub.2, or C.dbd.NOH--NH.sub.

Abstract: Interferon introduced parenterally in a human host or stimulated by an inducer (PICLC) for a period of greater than 21 days results in a major decrease in all markers of infectivity, such as DNA polymerase, and such markers remain at a depressed level during the period of treatment. Where PICLC is utilized to induce interferon in the host, a serum level of 50 units per milliliter or higher is necessary for effective clinical treatment and 17 .times. 10.sup.4 - 6.0 .times. 10.sup.3 U/kg/day is an effective dose for exogenous interferon. Especially long-term treatment with exogenous interferon of greater than 21 days and up to 14 months results in clinical improvement for chronic hepatitis B virus (HBV) infection and this long-term treatment has resulted in sustained improvement even after cessation of treatment as well as resulting in a decrease in infectivity risk to others in close proximity to the infected human host. Such clinical improvement is marked by normalization of liver histology.

Abstract: Tricyclic aromatic compounds of the formula ##STR1## including those wherein: (A) R.sub.1 is H, R.sub.2 is carbomethoxy, and R.sub.3 is methyl;(b) R.sub.1 is acetyl, R.sub.2 is carbomethoxy, and R.sub.3 is methyl;(c) R.sub.1 and R.sub.3 are methyl and R.sub.2 is carbomethoxy;(d) R.sub.1, R.sub.2, and R.sub.3 are hydrogen; and(e) R.sub.1 and R.sub.3 are methyl and R.sub.2 is hydrogenAre intermediates for the total synthesis of steroids.

Abstract: The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane)platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5.degree. C) of the desired product which is preferably utilized as the alkali metal salt.The 4-carboxyphthalato(1,2-diaminocyclohexane)-platinum(II) and alkali metal salts thereof may be combined in multiple drug regimen with substantially improved yield cures over the parent compound. For example, the compound denoted Pt-307 may be combined in a dual regimen with cyclophosphamide (CY) and in a triple drug regimen of Pt-307 plus cyclophosphamide (CY) and either 5-fluorouracil (5-FU) or hydroxyurea (HU) as the third component.

Abstract: The compound 6-amino-4-methyl-8-(.beta.-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c ]pyridazines-5'-phosphate (a nucleotide) as a new compound and its method of synthesis by phosphorylation of the known 6-amino-4-methyl-8-(.beta.-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c ]pyridazine (a nucleoside). The 5'-phosphate ester has utility against L-1210 mouse leukemia and has superior solubility over the parent compound which gives it a broader use pattern relative to dosage. This novel nucleotide also shows advantage in utilization as to pH over, for example, the hydrochloride salt which gives in solution a pH of 4 and is too acid for use.

Abstract: An electrode for implantation in the heart to control atrio-ventricular block by artificial pacemaker including plural electrically conductive wires grouped in a bundle with spring metal arcuate prongs formed on one end thereof. A sheath is provided to compress the prongs for insertion of the electrode through a cannula to place the electrode against the heart. The electrode is implanted in the heart by advancing the prongs through the pericardium into the myocardium.

Abstract: A therapeutic method of alleviating the symptoms and relieving intraocular pressure associated with open or wide-angle glaucoma which comprises administering a compound selected from diphenylhydantoin (DPH), mephenytoin, and ethotoin in an amount ranging from 200-900 mg per day preferably on a split or divided dosage basis for a period of 2-5 months. A preferred regimen for DPH is 100 mg three times per day.

Abstract: The purification of an endogenous composition isolated from mammalian brain tissue and termed enkephalin ("in the head"). Enkephalin is recovered from brain tissue by acetone solution and purified by means of column and thin layer chromatography. The composition which is a mixture of two pentapeptides, namely, (a) H-Tyr-Gly-Gly-Phe-Met-OH and (b) H-Tyr-Gly-Gly-Phe-Leu-OH wherein the ratio of a:b is from 3:1 to 4:1 has been found to be a non-addictive narcotic and an opiate agonist.The synthesis of the pentapeptide composition from the known structure above is accomplished by conventional solution techniques of protection of the amino groups, such as t-butyloxycarbonyl, benzyloxycarbonyl, and t-amyloxycarbonyl, or the solid phase peptide synthesis of R. Bruce Merrifield using a polymeric support and the same or similar amine protecting groups.

Abstract: An acousto-optical method and device for measuring the radiation produced by a transducer is described wherein such radiation is in the range of about 500 KHz to 10 MHz. The method consists of propagating ultrasound frequencies from the transducer through a transparent liquid medium in a cell, said cell having a transparent window or suitable device to provide a clear path for the radiation waves and passing a light through said cell at about a right angle to the direction of said ultrasound wherein the light is modulated in phase with the frequency of the ultrasound. The modulation of the light corresponding to the frequency of the ultrasound can be detected by a photo-cell measured and displayed on various devices. Further, a transducer can be calibrated absolutely using this method and apparatus from known constants and easily measured quantities. Moreover, it is readily adapted to measure the radiation of an unknown source to a known absolute source.

Abstract: A device and method for the concentration of parasite eggs and larvae consisting of separable upper and lower chambers connected by a mid-piece which incorporates a filter of stainless steel gauze. The sample is emulsified in the upper chamber and is filtered into the lower chamber. Ether is added through the upper chamber and the mid-piece and upper chamber are removed. The lower chamber is shaken and centrifuged, the mid-plug of debris is removed, and the tube is drained and swabbed clean leaving a small sediment containing the parasite eggs and larvae. The sediment is removed by extraction with Lugol's iodine or saline to dilute the sediment.

Abstract: The present invention consists of three process improvements in the so-called multi-step Piper-Montgomery process designed especially to produce the antifolate methotrexate which is closely related to both aminopterin and folic acid. 2,4,5,6-tetraaminopyrimidine sulfite is one starting material and is usually produced in the form of the bisulfite in an acetate buffer. The present modification positively produces the hydrochloride from the bisulfite and eliminates the acetate buffer utilized in prior art processes. Subsequently, a pteridine ring is formed from the pyrimidine hydrochloride using dihydroxyacetone at pH 5.5.+-.0.2 to form the second ring. This strict pH control together with the use of hydrochloride salt minus the acetate buffer assists in preferentially favoring the formation of 2,4-diamino-6-hydroxymethylpteridine.

Abstract: A process and resulting product for producing large unilamellar phosphatidylserine vesicles (LUV) in the diameter of about 2,000-12,000 A which may additionally encapsulate a drug. The large vesicles are prepared from an initial phosphatidylserine aqueous solution which is subjected to ultrasound or sonicated which produces small unilamellar vesicles (SUV) in the diameter range of 200-500 A. After the addition of calcium ion (Ca.sup.2+) in the molar concentration of about 1-10 mM (threshold 1-2 mM) and incubating for 30-60 minutes at room temperature above 10.degree. C and preferably 37.degree. C, intermediate cochleate lipid cylinders form. Finally, addition of a calcium chelating agent such as EDTA or EGTA to these cochleate cylinders produces by fusion the desired large closed spherical unilamellar vesicles (LUV). The intermediate cochleate form appears specific to the phospholipid serine utilized and to the calcium ion (Ca.sup.2+) incubating agent.

Abstract: A method of recovering a hormone from human blood plasma which has morphine agonist properties which comprises heating said plasma, extracting into butanol to recover anodynin, and purifying said anodynin by centrifuging and ion exchange column separation. Anodynin has a molecular weight of about 600.

Abstract: Tricyclic aromatic compounds of the formula ##STR1## including those wherein: A. R.sub.1 is H, R.sub.2 is carbomethoxy, and R.sub.3 is methyl;B. R.sub.1 is acetyl, R.sub.2 is carbomethoxy, and R.sub.3 is methyl;C. R.sub.1 and R.sub.3 are methyl and R.sub.2 is carbomethoxy;D. R.sub.1, R.sub.2, and R.sub.3 are hydrogen; andE. R.sub.1 and R.sub.3 are methyl and R.sub.2 is hydrogenAre intermediates for the total synthesis of steroids.

Abstract: An electrochemical crystal growth method wherein nutrient material (e.g., Ca(OH).sub.2) is continuously supplied to one electrode of a cell, is dissolved by electrolytic action, forming a concentration gradient, and concurrently is deposited (e.g., as Ca(OH).sub.2) near the other electrode in a predetermined amount dependent on the current through the cell. An electrolyte may be utilized which is selected from an aqueous mixture of an alkali metal salt and a soluble salt containing a metal ion in the product compound, crystals of which are to be grown. Alkaline earth hydroxides are preferred products and for growth of Ca(OH).sub.2 a preferred electrolyte is a mixture of calcium chloride and potassium chloride wherein the Ca.sup.2+ ion is regulated between 0.05-0.5 molar. A highly preferred electrolyte mixture is 0.5 molar KCl and 0.5 molar CaCl.sub.2 utilizing 1 mA current. The electrodes on the anode side may be constructed of any metal with low overvoltage for the oxidation of hydrogen (e.g.

Abstract: The compound 5,6-dihydro-5-azacytidine, 5AC[H], and non-toxic acid addition salts such as the hydrochloride, together with its preparation from 5-azacytidine (5-AC) by reduction of the 5,6-double bond of 5-AC with an alkali metal borohydride such as sodium borohydride. Additionally, 5,6-dihydro-5-azacytidine, 5AC[H], has antitumor activity for murine leukemia systems L1210 and P388 as an injectable. In comparison with the parent compound, 5-AC, the antitumor activity is comparable and 5AC[H] exhibits a more favorable therapeutic index. It also has better solution stability over a broad pH range. A structure for the HCl salt is given below.

Abstract: An artificial valve remotely placeable in a blood vessel without major surgery to supplant the function of a malfunctioning natural valve including an expansible check valve remotely placed in a constricted configuration through the vessel and a remotely removable constraint for selective expansion of the check valve for sealing engagement thereof within the walls of the vessel at the desired location.

Abstract: A method for identification of non-fermentative Gram-negative bacteria (NFB) consisting of correlating results from a plurality of oxidative alkalinization (OAL) assays in media samples consisting essentially of a minimal-protein medium, an indicator and a substrate and a plurality of oxidative acidification (OAC) assays in media consisting essentially of a minimal-protein medium, an indicator and a substrate. A medium for determining oxidative attack (OA) consists essentially of a minimal-protein medium, an indicator and a substrate.

Abstract: A method of producing thebaine from codeine and oripavine from morphine which comprises (a) producing the 0-6 methyl ethers from codeine and morphine using potassium hydride and methyl iodide as the O-alkylation agents and (b) subsequently oxidizing the respective 0-6 methyl ethers of codeine and morphine to shift from allylic structure to a dienol ether structure using an oxidizing amount of MnO.sub.2 in tetrahydrofuran to produce thebaine from codeine and oripavine from morphine. In the case of morphine, it is preferable to protect the 0-3 position by acetylation prior to the oxidizing step. Both the etherification and oxidizing steps are carried out under a protecting blanket such as nitrogen and the reactions are carried out preferably under atmospheric pressure and ambient temperature with the exception of the etherification affecting the 0-6 position which may be commenced by cooling with ice.