Abstract: Methods for treating cancer comprising administering a DLL4 antagonist and one or more anti-hypertensive agents are described. Also described are pharmaceutical compositions comprising a DLL4 antagonist and one or more anti-hypertensive agents, and kits comprising the same.

Abstract: Methods are described for slowing or inhibiting the progression of heart failure in a mammalian subject suffering from chronic hypertension. The methods involve administering an ?PKC, ?1PKC, or ?IIPKC peptide inhibitor, examples of which are provided.

Abstract: A specific and sensitive in vitro ELISA assay and diagnostic test kit is disclosed for determining levels of NT-proBNP protein in a variety of bodily fluids, non-limiting examples of which are blood, serum, plasma, urine and the like. The NT-proBNP ELISA assay test employs the sandwich ELISA technique to measure circulating NT-proBNP in human plasma. In order to obtain antibodies with specific binding properties for targeted amino acid sequences within human proBNP, recombinant human proBNP (or rhproBNP) was expressed and purified for use as an immunogen. Polyclonal antibodies (PAb) to specific amino acid sequences were subsequently purified from goat serum by sequential affinity purification. Monoclonal antibodies were raised against specific polypeptides. Recombinant human NT-proBNP (or rhNT-proBNP) was expressed and purified in order to obtain material for use in calibration of a quantitative method for measurement of human NT-proBNP.

Abstract: The present invention concerns an immunological test for determining NT-proBNP comprising at least two antibodies to NT-proBNP, wherein at least one of the antibodies to NT-proBNP is a monoclonal antibody. One of these antibodies is directed at least against parts of the epitope of NT-proBNP comprising the amino acids 38 to 50. In addition, one of these antibodies is directed at least against parts of the epitope of NT-proBNP comprising the amino acids 1 to 37 or 43 to 76. The epitope recognized by the antibodies can slightly overlap.

Abstract: Attenuated strains of Mycobacterium, particularly species of the tuberculosis complex, have the mycobacterial cell entry (mce) gene functionally disabled. The gene may be disabled by an insertion into the gene which disrupts the mycobacterial cell entry function thereof of a selectable marker which is used for screen for homologous recombinants in which a double cross-over event has been effected. The attenuated strains may be used in the immunization of hosts against Mycobacterium disease.

Abstract: Common human diseases like diabetes and hypertension have been demonstrated to possess an associated genetic component composed of numerous underlying genetic defects. Traditional positional cloning of genes which possess the mutations responsible for complex disease has been hindered by both the low statistical power each locus may afford, and by the technically-laborious nature of the positional cloning methodologies. Disclosed herein is a methodology for the rapid identification of the genes responsible for quantitative trait loci (QTL) comprised of comprehensive gene expression analysis in organs relevant to disease in combination with the positional mapping of known QTL, so as to quantitatively identify candidate genes. This aforementioned methodology was applied to a total of five tissues/organs derived from the spontaneously hypertensive rat (SHR), the stroke-prone variant of the SHR (SHR-SP) and control Wistar Kyoto rats (WKY).

Abstract: An antihypertensive agent containing an effective amount of dipeptide Tyr-Pro and/or a pharmaceutically acceptable salt thereof, the effective amount being from 0.05 to 10 mg/kg body weight/day, and a method for producing the same.

Abstract: Methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias are disclosed. Also disclosed are methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine cell hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject are disclosed, along with an antibody having binding specificity for ouabain.

Abstract: Compounds of general formula A--B--C in which: A is a monovalent radical of a L-ring molecule; B is a bivalent radical of a L-.alpha.-aminoacid; and C is a monovalent radical of a L-aromatic molecule. The compounds show an anti-hypertensive, analgesic, immuno-modulating and antiinflammatory activity, they are resistant to enzyme hydrolysis and they can be used for the preparation of drugs for oral administration.

Abstract: A class of broad spectrum bioactive polypeptides termed "Magainin" have been described. These peptides have a molecular weight of about 2500 or less, are highly water soluble, amphiphilic and non-hemolytic.

Abstract: Compounds of general formula A--B--C in which: A is a monovalent radical of a laevorotatory ring molecule; B is a bivalent radical of a laevorotatory .alpha.-aminoacid; and C is a monovalent radical of a laevorotatory aromatic molecule. The compounds show an anti-hypertensive, analgesic, immuno-modulating and antiinflammatory activity, they are resistant to enzyme hydrolysis and they can be used for the preparation of drugs for oral administration.

Abstract: This invention relates to new amino acid derivatives and pharmaceutically acceptable salts thereof, wherein the amino acid derivatives are useful in the treatment and/or prevention of hypertension, heart failure, renal diseases or glaucoma.

Abstract: Phosphorus containing polypeptides as renin inhibitors, useful as antihypertensive agents.

Abstract: The invention concerns novel renin-inhibitory compounds which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism, glaucoma, and diseases caused by retroviruses including HTLV-I -II, and -III. Processes for preparing the compounds, novel intermediates useful in the preparation thereof, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, congestive heart failure, or hyperaldosteronism.

Abstract: New amino acid derivatives of the formulaR.sup.1 --Z--NR.sup.2 --CHR.sup.3 --CR.sup.4 --(CHR.sup.5).sub.a --CO--E--Q--Ywherein R.sup.1 to R.sup.5, a, Z, E, Q and Y have the meanings defined herein, and salts thereof inhibit the activity of human plasma renin.

Abstract: Novel amino acid derivatives of the formula IX--Z--NH--CHR.sup.1 --CO--NR.sup.2 --CHR.sup.3 --CR.sup.4 --(CHR.sup.5).sub.n --CO--E--W'--Ywherein X, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, E, W', Y and n have the meanings defined herein and their salts inhibit the activity of human plasma renin.

Abstract: A new circulating factor from the parathyroid gland of some hypertensive mammals have been isolated and characterized. Polyclonal and monoclonal antibodies raised against this factor are usable as a screen for the presence of the factor. The factor is involved in the control of calcium uptake in cells. Hypertensive mammals may be treated to lower mean blood pressure by administering a calcium channel blocking agent together with one or both of a calcium supplement and Vitamin D. The hypotensive effect of this combination is synergistic and the dose response is more predictable than the administration of any of these agents singly. The factor has a molecular weight of 3,000 to 4,000 Daltons.

Abstract: A pharmaceutical composition comprising a solution of a tenin inhibitor of the formula: ##STR1## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl;R.sub.2 is benzyl, p-methoxybenzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl;R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH.sub.3 S-- or CH.sub.3 SCH.sub.2 --;R.sub.4 is loweralkyl or cyclopropyl;R.sub.5 is hydrogen or loweralkyl; andX is CH.sub.2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof in a pharmaceutically acceptable solvent, said solution being encapsulated in a soft elastic gelatin capsule.

Abstract: Cyclic pentapeptides of the formula:cyclo (-X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -X.sup.5 -) (I)wherein X.sup.n (n=1-5) represents amino acid residues. These compounds are useful as hypotensive drugs.

Abstract: A new compound, which we have named "Leualacin" has the formula (I): ##STR1## and may be prepared by cultivation of a microorganism of the genus Hapsidospora, especially Hapsidospora irregularis. The compound may be used for the treatment and prophylaxis of cardiovascular diseases and disorders, especially hypertension.

Abstract: Tripeptides having hypotensive activity, defined by the following general formula:A--B--C--OZ (I)wherein:A represents a residue of L-pyroglutamic acid, L-proline of L-proline bearing a substituent on its amino group ##STR1## wherein R.sub.1 is an acyl with a number of carbon atoms in straight chain not higher than 9, a benzyloxycarbonyl group or an alkyloxycarbonyl group;B is an .alpha.-aminoacide residue derived from one of the natural aminoacids;C is a residue of L-tryptophan (Trp), of L-phenylalanine (Phe) or of L-tyrosine (Tyr);Z is a hydrogen atom or an alkyl group with a number of carbon atoms in straight chain not higher than 9.

Abstract: Compounds of the formula ##STR1## wherein R.sub.1 is an N-heterocyclic group as defined herein and Y can be --NH--, --O-- or --CH.sub.2 --, are disclosed. These compounds are inhibitors of renin and therefore useful as cardiovascular agents.

Abstract: The invention concerns novel AVP-binding peptides having the formula:Thr-Met-X-Val-Leu-Thr-Gly-Ser-Pro-Bwherein X is selected from the group consisting of Lys, Arg, and Asp; B is OH, NH.sub.2, NHAlK, wherein Alk is lower alkyl of 1-4 carbons, inclusive. These peptides block AVP function, and, therefore, are useful in many areas among which is the control of hypertension.

Abstract: The present invention provides novel renin-inhibiting peptides of the formula X-A.sub.6 -B.sub.5 -C.sub.8 -D.sub.9 -E.sub.10 -F.sub.11 -G.sub.12 -H.sub.13 -I.sub.14 -Z, wherein X and Z are terminal groups, C.sub.8 contains S-aryl-D- or L- or DL-cysteinyl, 3-(arylthio)lactic acid, and 3-(arylthio)alkyl moieties, and the remaining variables are amino acid residues. Such inhibitors are useful for the diagnosis and control of renin-dependent hypertension.

Abstract: A composition and method for treating thrombotic disorders. The composition comprises a peptide comprising an amino acid sequence corresponding to the sequence of the amino acid residues in the EGF domain of Factor IX, or a subsequence thereof. Such peptides compete with coagulation Factors IX and IXa for endothelial binding cites and thereby inhibit thrombosis formation.

Abstract: Compounds of the formula ##STR1## in which R.sub.1 represents hydrogen or acyl, X.sub.1 represents an optionally N-alkylated amino acid residue that is bonded N-terminally to R.sub.1 and C-terminally to X.sub.2, X.sub.2 represents an optionally N-alkylated amino acid residue that is bonded N-terminally to X.sub.1 and C-terminally to the group -NR.sub.2 -, R.sub.2 represents hydrogen or lower alkyl, R.sub.3 represents hydrogen, alkyl, cycloalkyl, aryl-lower alkyl or aryl, R.sub.4 represents hydroxy or etherified or esterified hydroxy, R.sub.5 represents alkyl, cycloalkyl, aryl-lower alkyl or aryl, and R.sub.6 represents free or substituted amino or substituted hydroxy, and salts of such compounds having salt-forming groups inhibit the blood pressure-increasing action of the enzyme renin and can be used as anti-hypertensives.

Abstract: Antihypertensive compounds with angiotensin-converting enzyme inhibitory activity and diuretic activity are disclosed. Such compounds are useful in the treatment of cardiovascular disorders, especially hypertension and congestive heart failure, and are useful in the treatment of glaucoma.

Abstract: The invention relates to renin inhibiting compounds of the formula ##STR1## wherein A is hydrogen; loweralkyl; arylalkyl; Or.sub.10 wherein R.sub.10 is hydrogen or loweralkyl; NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are independently selected from hydrogen and loweralkyl; or R.sub.13 --CO--B wherein B is NH, O, CH.sub.2, HNCH.sub.2 and R.sub.13 is loweralkyl, alkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, N-protected aminoalkyl, hydroxylated dialkylamino, (heterocyclic)alkyl or a substituted or unsubstituted heterocyclic, carboxyalkyl, or lower alkyl carboxyalkyl esters; W is N or CH: U,V may be the following combinations H,OH; OH,H; H,H; or when taken together as O represents a carbonyl with the provisos that if U,V.dbd.H,OH, then W=CH, and if U,V.dbd.O then W.dbd.N; R.sub.1 , R.sub.3 and R.sub.5 are loweralkyl or hydrophilic, lipophilic or aromatic amino acid side chains and may be the same or different; R.sub.2, R.sub.4, R.sub.7, R.sub.8 and R.sub.

Abstract: New decapeptides having hypotensive action are disclosed, which can be defined by the formula:GLp-Leu-Trp-Pro-X-Pro-Y-Z-Pro-Pro-OH (I)wherein:X=Arg or OrnY=His or GlnZ=Ile or Valwith the following limitations:whenX=Arg:Y=HisZ=Val;whenX=Orn:Y=GlnZ=Ile;or, whenX=Orn:Y=HisZ=Valand pharmaceutically acceptable salts, amides of alkyl esters thereof.

Abstract: (Benzothiadiazine, benzamido and benzenesulfonyl)phenyl-substituted carboxyalkyl dipeptide compounds are disclosed. Compounds of this invention are useful as antihypertensive agents.

Abstract: Analgesic and hypotensive activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, alkyl, carboxyalkyl, halo substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl, or heteroaryl;R.sub.3 is hydroxy, alkoxy, (substituted alkyl)oxy, arylalkoxy, (heteroaryl)alkoxy, or --NY.sub.1 Y.sub.2, wherein Y.sub.1 and Y.sub.2 are each independently hydrogen, alkyl, aryl, or arylalkyl, or Y.sub.1 is hydrogen and Y.sub.2 is substituted alkyl or (heteroaryl)alkyl;A.sub.1 is glycyl, alanyl, leucyl, phenylalanyl, arginyl, sarcosyl, seryl, asparagyl, lysyl, glutamyl, histidyl, tryptophyl, cysteinyl, methionyl, threonyl, tyrosyl, leucyl, valyl, aspartyl, prolyl, norleucyl, norvalyl, or ##STR2## wherein n.sub.6 is an integer of 2 to 15; A.sub.2, A.sub.3, A.sub.4 and A.sub.

Abstract: Dipeptides having the formula ##STR1## wherein A is halogen, hydrogen, lower alkyl, or lower alkoxy; B is hydrogen or lower alkyl, or A and B are taken together to form an ortho-methylene or ethylene bridge; R is hydrogen, lower alkyl, or phenylalkyl; and X.sup.1 and X.sup.2 are independently chosen from hydroxy or lower alkoxy; are inhibitors of angiotensin-converting enzyme and can be used for the treatment of hypertension in mammals.

Abstract: Compounds of the formula ##STR1## and their pharmaceutically acceptable salts, wherein the substituents are as defined herein, having antihypertensive activity.

Abstract: What are disclosed are indole, quinoline and isoquinoline compounds of the formula ##STR1## in which n denotes 0 or 1, m denotes 1 or 2, but (n+m).ltoreq.2, A together with the bridgehead carbon atoms denotes a benzene or a cyclohexane ring, Y.sub.1 denotes hydrogen, lower alkanoyl or lower cycloalkanoyl, benzoyl nicotinoyl or a radical of the formula II, and Y.sub.2 denotes methyl, amino, lower alkanoylamino, lower cycloalkanoylamino, benzoylamino or nicotinoylamino, and salts thereof, useful as hypotensive agents, and methods for making the same.

Abstract: Peptides of the formula ##STR1## wherein X is various amino or imino acids or esters are useful as hypotensive agents.