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Biomedical subjects

G J Moore

Publications and source records attributed to G J Moore.

At least 145 records · Page 8Linked to original sources
PubMed1979

Synthesis of angiotensin II antagonists containing sarcosine in position 7.

Analogues of the type [1-sarcosine,7-sarcosine, 8-X]angiotensin II, where X = isoleucine, leucine, alanine, methionine, O-methylthreonine, or DL-alloisoleucine, were synthesized by the solid-phase method and purified by partition chromatography, cation-exchange chromatography, and high-pressure liquid chromatography. In the isolated rat uterus, these analogues had activities of less than 0.1, less than 0.1, less than 0.1, less than 0.1, less than 0.1, and 0.7%, respectively, of the hyotropic activity of angiotensin II and inhibited the contractile response to angiotensin II with pA2 values of 8.1, 7.2, 6.7, 7.7, 7.4, and 8.4, respectively. In the vagotomized ganglion blocked rat, the analogues had 0.7, 0.21, 0.06, 0.72, 0.13, and 12.5%, respectively, of the pressor activity of angiotensin II.

Angiotensin II↗
PubMed1979

Antagonists of angiotensin II containing N-methyl-L-alanine and DL-nipecotic acid in position 7.

[1-sarcosine, 7-N-methyl-L-alanine, 8-isoleucine]-Angiotensin II and [1-sarcosine, 7-DL-nipecotic acid, 8-isoleucine]-angiotensin II were synthesized by the solid-phase method and purified by cation-exchange chromatography and high-pressure liquid chromatography. In the isolated rat uterus these analogs and less than 0.1% of the myotropic activity of angiotensin II and inhibited angiotensin II with pA2 values of 8.2 and 7.8, respectively. In the rat pressor assay (vagotomized ganglion blocked rat) these analogs had 0.9 and 2.8%, respectively, of the pressor activity of angiotensin II. The results show that the proline residue in position 7 of [Sar1,Ile8]-angiotensin II may be replaced by other secondary amino acids without disrupting interactions at angiotensin II receptors.

Amino Acid Sequence↗
PubMed1979

Conjunctivitis in the nude rat (rnu/rnu).

Nude rats are susceptible to similar eye problems to those suffered by nude mice, notably conjunctivitis leading to periorbital abscesses. Pasteurella pneumotropica has been isolated from the conjunctiva. The condition can be alleviated by washing the eyes of mildly affected rats with warm water. More severe cases respond to treatment with ampicillin. Conjunctivitis has not appeared in a germ-free colony of nude rats.

Animals↗
PubMed1979

Allergic encephalitis, rabies antibodies, and the blood/brain barrier.

Similarity of the syndromes of rabies and of encephalomyelitis resulting from rabies vaccination poses a problem in differential diagnosis that has had tragic consequences. That difficulty may also be largely responsible for the traditional belief that rabies is inexorably fatal, in that recovery from paralysis is interpreted as evidence that the disease was postvaccinal encephalomyelitis rather than rabies. Diagnosis is additionally complicated by presence of rabies antibodies in serum in both conditions. However, we have found that rabies antibodies elicited by vaccination do not pass the blood/brain barrier to enter the fluids of the CNS in EAE, the experimental counterpart of postvaccinal encephalomyelitis; whereas antibodies are present in high titer as a result of production in situ after recovery from rabies. Therefore a ratio of antibody concentrations of greater than 1:10 in CSF and serum indicates chronic rabies or recovery from that disease.

Animals↗
PubMed1978

Effect of the basic amino-acid side chain length and the penultimate residue on the hydrolysis of benzoldipeptides by carboxypeptidase B.

The kinetic parameters Km and k cat/K m have been determined for the carboxypeptidase B (CPB, EC 3.4.12.3) catalyzed hydrolysis of benzoylglycyl-DL-homolysine and benzoylglycyl-L-homorginine. Plots of these data and those for Bz-Gly-Orn and Bz-Gly-Arg (Wolff, E. C., Schirmer, E.W. & Folk, J. E. (1962) J. Biol. Chem. 237, 3094-3099) and Bz-Gly-Lys versus the length of the side chain of the basic amino acid indicate that unlike trypsin (EC 3.4.21.4) (Seely, J. H. & Benoiton, N. L. (1970) Can. J. Biochem. 48, 1122-1131) CPB has a higher bending affinity for a guanidino group than for an amino group at the side chain of the substrate C-terminus. On the other hand, CPB is similar to trypsin (ibid) in that the best substrate would have a side chain length between those of lysine and arginine. Studies with Bz-MeGly-Lys and Bz-Ala-Lys showed that the former is very slowly hydrolyzed by CPB but that the latter is a good substrate with a high affinity for the enzyme, indicative of considerable participation of the Calpha-methyl group of alanine in the binding of the substrate to the enzyme.

Benzoates↗
PubMed1977

Differences in efficiency of protective effect caused by high ambient temperature in mice infected with diverse substrains of rabies virus.

We have shown previously that a non-fatal outcome of infection with street rabies virus occurs more often when mice are exposed to a high ambient temperature (HAT = 35 degrees C) early in the course of the infection. To determine what influence the virus strain had on this protective effect of HAT, we have extended these observations to studies of a fixed rabies strain, CVS and several substrains of CVS virus derived from temperature-sensitive (ts) mutants. In all cases, mortality was reduced to some extent by exposure of the animals to HAT; however, dramatic strain-specific differences in the extent of the effect were noted. Although each of the virus substrains tested was revertant in the ts character (as tested in vitro using a non-permissive temperature of 40-5 degrees C), several substrains (ts 1, ts 4, RT51) caused disease that was sensitive (greater than 90% reduction in mortality) to HAT. Mortality induced by the parental CVS virus was reduced approx. 50% at HAT. A single CVS virus substrain, VSW89, caused disease that wal less affected by HAT than was disease induced by the parental strain. As in previous studies with street virus, the incubation periods for infection with CVS virus substrains were consistently prolonged at HAT.

Animals↗
PubMed1975

Effect of modifiers on the hydrolysis of basic and neutral peptides by carboxypeptidase B1.

The initial rates of hydrolysis of Bz-Gly-Lys and Bz-Gly-Phe by carboxypeptidase B (CPB) are increased in the presence of the modifiers beta-phenylpropionic acid, cyclohexanol, Bz-Gly, and Bz-Gly-Gly. The hydrolysis of the tripeptide Bz-Gly-Gly-Phe is also activated by Bz-Gly and Bz-Gly-Gly, but none of these modifiers activate the hydrolysis of Bz-Gly-Gly-Lys, Z-Leu-Ala-Phe, or Bz-Gly-phenyllactic acid by CPB. All modifiers except cyclohexanol display inhibitory modes of binding when present in high concentration. Examination of Lineweaver-Burk plots in the presence of fixed concentrations of Bz-Gly has shown that activation of the hydrolysis of neutral and basic peptides by CPB, as reflected in the values of the extrapolated parameters, Km(app) and kcat, occurs by different mechanisms. For Bz-Gly-Gly-Phe, activation occurs because the enzyme-modifier complex has a higher affinity than the free enzyme for the substrate, whereas activation of the hydrolysis of Bz-Gly-Lys derives from an increase in the rate of breakdown of the enzyme-substrate complex to give products. Cyclohexanol differs from Bz-Gly and Bz-Gly-Gly in that it displays no inhibitory mode of binding with any of the substrates examined, activates only the hydrolysis of dipeptides by CPB, and has a greater effect on the hydrolysis of the basic dipeptide than on the neurtal dipeptide. Moreover, when Bz-Gly-Lys is the substrate, cyclohexanol activates its hydrolysis by CPB by increasing both the enzyme-substrate binding affinity and the rate of the catalytic step, an effect different from that observed when Bz-Gly is the modifier. The anomalous kinetic behavior of CPB is remarkably similar to that of carboxypeptidase A, and is a good indication that both enzymes have very similar structures in and around their respective active sites. A binding site for activator molecules down the cleft of the active site is proposed for CPB to explain the observed kinetic behavior.

Animals↗
PubMed1975

Effect of Nepsilon-alkylation of the substrate on the hydrolysis of benzoylglycyl-L-lysine by carboxypeptidase B1.

The action of carboxypeptidase B (EC 3.4.12.3) on the benzoylglycyl dipeptides Bz-Gly-Lys(X) where X = methyl, ethyl, propyl, formyl, dimethyl, isopropyl, trimethyl, and benzyl has been investigated. All were hydrolyzed, at a rate decreasing in the order indicated, except where X = trimethyl and benzyl. Compounds where X = dimethyl, formyl, and isopropyl were hydrolyzed very slowly, and did not inhibit the hydrolysis of Bz-Glys-Lys by the enzyme. The kinetic parameters kcat and Km were determined for compounds with X = methyl and ethyl. The observed decrease in rate of hydrolysis of substrates with increasing size of X is consistent with increasing steric hindrance effects arising from the interaction of the Nepsilon-alkyl group with residues of the protein in the cleft which accommodates the substrate side-chain, and resulting in weaker binding of the substrate. Bz-Gly-Lys(Me2) was prepared by reductive methylation of Bz-Gly-Lys. Bz-Gly-Lys(Me3) was prepared by the reaction of Bz-Gly-Lys(Me2) with diazomethane in aqueous solution. Bz-Gly-Lys(Me) and Bz-Gly-Lys(Et) were synthesized by classical coupling procedures from the appropriately protected lysine derivatives.

Alcohols↗
PubMed1974

Effects of high ambient temperature on various stages of rabies virus infection in mice.

Effects of high ambient temperatures on various stages of rabies virus infection have been studied. Ambient temperature increased within the tolerated range was found to have little effect upon body temperature of normal mice, but caused marked elevation of temperature during illness. Temperatures at onset of patent illness in mice were lower than normal. Increased body temperature in the higher thermic ambience during the incubation period was associated with decreased mortality and frequent abortive infections. Exposure to high ambient temperature late in the incubation period delayed onset of illness, decreased mortality, and increased frequency of abortive infections, but exposure to high ambient temperature after onset of patent illness did not affect the course of the disease.

Animals↗