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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 343 records · Page 19Linked to original sources
PubMed1977

Pharmacological effects of introducing a double bond into a binding site of oxytocin. Analogues with L-3,4-dehydroproline in position 7.

The side chain of the proline residue in position 7 of oxytocin has been proposed as a binding site of the hormone for the uterotonic receptor. This is the first in a series of studies in which the possibility is explored that amino acid residues located at such sites and bearing unsaturated side chains may contribute more strongly to binding than neutral, aliphatic side chains. To test this hypothesis [7-(L-3,4-dehydroproline)]oxytocin, [1-beta-mecaptopropionic acid,7-(L-3,4-dehydroproline)]oxytocin, and [1-L-alpha-hydroxy-beta-mercaptopropionic acid,7-(L-3,4-dehydroproline)]oxytocin were prepared by the solid-phase technique of peptide synthesis. Some of the pharmacological properties of the analogues were determined, and the following specific activities, respectively, were found: rat uterotinic, 1071 +/- 59, 1066 +/- 95, 880 +/- 180; avian vasodepressor, 548 +/- 10, 1008 +/- 42, 1295 +/- 62; rat antidiuretic 5.9 +/- 0.2, 23.3 +/- 1.1, 76.7 +/- 2.3. All analogues possess a lower rat pressor activity than ocytocin. Compared to oxytocin, [7-(L-3,4,-dehydroproline)]oxytocin exhibits a parallel displacement of the cumulative uterotonic log dose vs. response curve toward lower concentration (pD2 = 9.26 vs. 8.63) but elicits the same maximum response. These data would seem to support the hypothesis that the introduction of unsatuation into binding element of a peptide hormone can enhance the affinity of the hormone for some of its receptors and thereby its selectivity.

Animals↗
PubMed1977

Explanation of the observation of pancreatic ribonuclease activity at pH 4.5.

A recent conclusion that beef pancreas contained a molecular species of ribonuclease with intrinsically high activity at pH 4.5 has been found to be incorrect. The particular assay used in the earlier experiments gives anomalous results at acid pH in the presence of low concentrations of ions such as phosphate which was used during the fractionation. By turning to the more widely employed form of the perchloric acid precipitation assay, interference is avoided and the ribonuclease in beef pancreas is confirmed as consisting almost completely of the molecular species well-characterized as ribonuclease A. The clarification of the assay question permits a clear interpretation of the results of each step of the chromatographic purification procedure that led to the initial conclusion, including an artifact that arose when gel filtration was attempted with distilled water rather than with buffer.

Animals↗
PubMed1977

A further example of human blood group chimaerism.

Blood group chimaerism was detected in a healthy fertile woman, not known to be a twin. Her peripheral lymphocytes had a male karyotype (46/XY); fibroblasts cultured from her skin had a female karyotype (46/XX). The mechanism of chimaerism could not be established.

ABO Blood-Group System↗
PubMed1977

Resolution of lipid-containing atherosclerotic lesions induced by injury.

In previous experiments, injury-induced atherosclerosis has been shown to be associated with the development of fatty streaks. The findings suggested that fatty streaks might represent a stage in healing of intimal injury evolving to fibrous plaques, free of lipid. The present experiment was designed to study the incidence and evolution of these lesions during a 2-week period of lesion retrogression following removal of a catheter placed in the aorta for 1 week. The findings indicate that as fat-containing lesions, either of the thromboatherosclerotic or fatty streak varieties, decreased, the amount of nonlipid-containing fibrous lesions increased.

Animals↗
PubMed1977

The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle cell proliferation and re-endothelialization.

This study was designed to investigate the mechanisms involved in fibromusculoelastic lesion formation produced by selective de-endothelialization by the intra-arterial balloon catheter technique in thrombocytopenic rabbits. Thrombocytopenia was induced and maintained for up to 30 days by daily injections fo highly specific sheep anti-rabbit platelet sera (APS). Evidence for re-endothelialization was obtained by i.v. Evans blue dye 30 min before sacrifice. Rabbits received daily injections of APS, which reduced the mean platelet count to 5,600/cm3; control animals received identically treated normal sheep sera on the same schedule, and had mean daily platelet counts of 363,000/cm3. Evaluation of intimal thickness was assessed by counting cell layers in semithin sections. Intimal thickening in aortae from rabbits treated with APS was strikingly suppressed, in contrast to those from normal sheep sera-treated animals which showed a mean intimal thickness of 18 cell layers within 28 days often after de-endothelialization. Re-endothelialization was not affected by APS treatment. These results indicate that the proliferation of smooth muscle cells is dramatically inhibited by reduction of platelets.

Animals↗
PubMed1977

Dieldrin residues in soybeans in Illinois, 1965, 1966, 1967, 1971, and 1974.

The Illinois soybean crop was monitored in 1965, 1966, 1967, 1971, and 1974 for dieldrin residues resulting from aldrin applied to corn in the years before soybean cultivation. Residue levels of dieldrin in soybeans increased between 1965 and 1974. The percent of fields which had soybeans with a dieldrin level above 0.03 ppm increased between 1965 and 1974. Dieldrin residue levels in soybeans grown in Illinois are expected to decline now that the use of aldrin has diminished and will soon cease. No significant correlation was evident between the dieldrin levels in soybeans and the area of the State where they had grown, the date of planting, or the variety.

Acetonitriles↗
PubMed1977

Platelets, thrombosis and atherosclerosis.

The interaction of platelets with the vessel wall can contribute to the early stages in the development of atherosclerosis through effects on smooth muscle cell proliferation, endothelial permeability, and possibly by causing vessel wall injury. Platelets are involved in the development of thrombi in response to vessel injury, and the repeated formation of platelet emboli and platelet-fibrin emboli from the mural thrombi may be one of the factors that cause clinical complications of atherosclerosis. Drugs which inhibit platelet function, particularly those that prolong shortened platelet survival (sulfinpyrazone and dipyridamole) may prove to be important in inhibiting the response of blood to vessel injury and thereby modifying the extent of atherosclerosis and its complications.

Arteries↗
PubMed1976

Inhibition of injury induced thromboatherosclerotic lesions by anti-platelet serum in rabbits.

We have previously shown that repeated or continuous intimal injury caused by an indwelling aortic catheter causes a variety of lesions in rabbits maintained on a diet unsupplemented by lipid. These include fatty streaks, lipid-free fibrous plaques and lipid-rich raised thromboatherosclerotic plaques. Whether lipid-rich raised lesions are a result of injury or co-existing thrombosis or both is not clear. The present experiment was designed to answer this question. Anti-platelet serum (APS) to washed sonicated rabbit platelets was raised in sheep. PE 60 polyethylene catheters were placed in the aortas of 35 rabbits by way of a femoral artery. The animals were randomly divided into 2 groups. The experimental group (17 rabbits) received an intravascular injection of 1.0 ml of APS followed 8 hours later by a subcutaneous injection of 0.5 ml. Thereafter, 0.5 ml APS was given subcutaneously each day for 13 additional days. The control group (18 rabbits) received no APS. Platelet counts were done prior to surgery, at 5 minutes following surgery, at 4 days, 8 days and just prior to killing. Extent of lesions was estimated by photographing the opened aortas, projecting the photographs on cardboard, cutting out the areas occupied by the different lesions and weighing the cardboard. The mean weight of raised lesions in the control group was 6 to 7 times greater than in the experimental groups. Statistical analysis of this difference based on Welsh's "t" test for unequal variances was highly significant (P less than 0.001). Platelet counts in the experimental groups varied from 0 to 20,000 at 14 days. In animals with platelet counts less than or equal to 1,000 mm3 raised lesions were completely prevented. In a second experiment the effect of APS was compared with normal sheep serum (NSS). A similarly significant inhibition of raised lesions occurred in the APS group. The extent of lesions in the NSS control was similar to that in the No-APS group of the first experiment. These findings indicate that thrombosis is more important than injury in the development of lipid-rich raised lesions.

Animals↗
PubMed1976

Preparation of cross-linked dimers of pancreatic ribonuclease.

The cross-linking reaction between diimido esters and ribonuclease has been studied in terms of the yield of cross-linked dimer with optimum activity toward double-stranded RNA. With dimethyl suberimidate the most satisfactory conditions were condensation for 15 min at pH 7.5-8.0 at 21 degrees C with 1.25 mol equiv of the diimido ester and a protein concentration of 6%. The dimer (yield 20%) had 19 unmodified NH2 groups out of a theoretical 20 for a molecule in which two such groups are involved in the cross-linkage; the activity toward poly(A)-poly(U) in 0.14 M salt solution by spectrophotometric assay was 8.5 times that of the monomeric enzyme toward the same substrate.

Animals↗
PubMed1976

Synthesis and some properties and antitumor effects of the actinomycin lactam analog, (di(1-L-alpha, beta-diaminopropionic))actinomycin D1.

A lactam analog of actinomycin D (AMD) has been synthesized as a potential antitumor chemotherapeutic agent. Both L-threonine residues were replaced by L-alpha,beta-diaminopropionic acid. Starting with Nalpha-benzyloxycarbonyl-Nbeta-tert-butyloxycarbonyl-L-alpha,beta-diaminopropionic acid methyl ester hydrochloride the linear intermediate Nalpha-benzyloxycarbonyl-Nbeta-(tert-butyloxycarbonylsarcosyl-L-N-methylvalyl)-L-alpha,beta-diaminopropionyl-D-valyl-L-proline p-nitrophenyl ester was prepared by conventional methods of peptide synthesis in solution. Selective cleavage of the Nbeta-tert-butyloxycarbonyl group and lactam formation afforded the desired cyclic pentapeptide derivative. The chromophore precursor, Nalpha-(2-nitro-3-benzyloxy-4-methylbenzoyl) substituent, was introduced via its symmetric anhydride. Catalytic reduction followed by ferricyanide-mediated phenoxazinone formation provided the lactam analog, [di(1'-L-alpha,beta-diaminopionic acid)]actinomycin D ([Dpr1]2-AMD). Its binding to natural and synthetic DNA and that of an analogous L-threo-alpha,beta-diaminobutyric acid containing lactam ([Dbu1]2-AMD) compared with the binding of AMD (in which the peptides are in lactone form) was studied by circular dichroic (CD) spectroscopy. The visible and uv CD spectra of free AMD differed from those of the free lactam analogs, indicating that the asymmetric environment of the pentapeptide rings in the region of the chromophore differs in free actinomycin lactone and lactams. In the presence of calf thymus DNA, PM2 DNA, and the synthetic d(A-T)-like copolymers containing 2,6-diaminopurine (DAP), poly[d(DAP-T)], and poly[d(DAP-A-T)], the rotational strengths of the optically active transitions in the visible region of the actinomycins increased, and the CD spectra in the presence of the various DNA duplexes were qualitatively similar. The CD spectra of bound actinomycin lactams resembled the spectrum of bound AMD. This suggests that the lactone and lactam actinomycins acquire a similar environment when bound to DNA. [Dpr1]2-AMD was less cytotoxic than AMD in antibacterial assays but exhibited somewhat higher toxicity in mice than AMD. At optimal dose levels the lactam analog had little or no antitumor activity in three murine tumor systems.

Animals↗