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Biomedical subjects

C M Baugh

Publications and source records attributed to C M Baugh.

At least 37 records · Page 2Linked to original sources
PubMed1979

Differential inhibition of host and viral thymidylate synthetases by folylpolyglutamates.

The ability of folate analogues to inhibit host and viral thymidylate synthetases was measured using the corresponding Escherichia coli and T2-phage-induced enzymes. In the absence of Mg2+, 6 x 10(-7) M pteroylhexaglutamate inhibited the T2-phage-induced synthetase by 50%, but at least 100-fold greater levels of this compound were necessary to inhibit the E. coli synthetase by this amount. At 2.5 x 10(-6) M pteroylhexaglutamate, at least 80% inhibition of the T2-phage synthetase could be obtained with little or no inhibition of the E. coli enzyme. The pteroylmonoglutamate was about 2 orders of magnitude less inhibitory towards the T2-phage enzyme than the pteroyltri- to -heptaglutamates. However, upon addition of Mg2+ to the assay mixture, the inhibition produced by pteroylhexaglutamate was essentially reversed, with the E. coli synthetase now increasingly inhibited by this compound and the T2-synthetase only minimally impaired. Methotrexate and N10-formyl-2-amino-4-hydroxyquinazoline, although inhibitory to both enzymes in the presence or absence of Mg2+, did not show this differential selectivity. These results suggest that certain folate analogues may be useful in distinguishing between a host and an infecting organism's thymidylate synthetase and could thus provide an additional means of screening for potential chemotherapeutic agents.

Coliphages↗
PubMed1979

Structural role of the polyglutamate portion of the folate found in T4D bacteriophage baseplate.

Three types of reagents were used to determine the structural role and location of the polyglutamate portion of the Escherichia coli T4D bacteriophage baseplate dihydropteroyl hexaglutamate. These reagents were examined for their effect in vitro on some of the final steps in phage baseplate morphogenesis. The reagents were (i) a series of oligopeptides composed solely of glutamic acid residues but with various chemical linkages and chain lengths; (ii) a homogeneous preparation of carboxypeptidase G1, an exopeptidase that hydrolyzes carboxyl-terminal glutamates (or aspartates) from simple oligopeptides, including the gamma-glutamyl bonds on folyl polyglutamates as well as the bond between the carboxyl group of the p-aminobenzoyl moiety and the amino group of the first glutamic acid residue of folic acid; and (iii) antisera prepared against a polyglutamate hapten. All three types of reagent markedly inhibited the attachment of the phage long tail fibers to the baseplate. Other steps in baseplate assembly such as the addition of T4D gene 11 or gene 12 products were not affected by any of these reagents. These results indicate that the polyglutamate portion of the folate is located near the attachment site on the bacteriophage baseplate for the long tail fibers.

Carboxypeptidases↗
PubMed1979

Plasma clearance and plasma half-disappearance time of exogenous thyrotropin-releasing hormone and pyroglutamyl-N3im-methyl-histidyl prolineamide.

The plasma clearance rate (PCR) and plasma half-disappearance time (t1/2) of TRH was compared to the PCR and t1/2 of pyroglutamyl-N3im-methyl-histidyl prolineamide (methyl-TRH), a more potent analog of TRH in normal subjects. The PCR for TRH was 1500 +/- 329 (SD) ml/min, which was significantly greater than the PCR of methyl-TRH (783 +/- 96 ml/min). The t1/2 of TRH was 6.2 min compared to a t1/2 of 11.5 min for methyl-TRH. The slower clearance of methyl-TRH is probably due to the increased resistance to degradation by serum enzymes of methyl-TRH compared to TRH.

Half-Life↗
PubMed1976

Effect of N3im-methyl-thyrotropin releasing hormone on the human pituitary-thyroid axis.

The N3im-methyl analogue of thyrotropin release hormone (methyl-TRH) was compared with TRH as a thyrotropin releaser in 30 euthyroid volunteers (ages 19-61 years). The mean TSH response to 100 mug of methyl-TRH was greater (P less than 0.005) than the TSH response to 500 mug of TRH from 10 min to 240 min after giving the releasing factors. The mean peak TSH (at 30 min), maximum deltaTSH, and integrated TSH response area were greater (P less than 0.005) after administration of methyl-TRH than after TRH. The TSH response to methyl-TRH was significantly greater (P less than 0.05) for the 11 females than for the 19 males in this study. The mean baseline TSH was correlated with the maximum deltaTSH (r = 0.72, P less than 0.01) after methyl-TRH stimulation. The mean serum T3 concentration after methyl-TRH was significantly elevated at 60 min, peaked at 210 min and remained significantly elevated at 240 min. The peak serum T3, maximum T3 and T3 response area were significantly greater (P less than 0.005) after giving methyl-TRH than after TRH. The methyl-TRH induced T3 response area was 1.4 times the TRH induced T3 response area. The serum T4 concentration after methyl-TRH was elevated at 90 min (P less than 0.005), reached a peak at 210 min, and at 240 min was still 1.25 times the mean baseline T4. The peak serum T4, maximum deltaT4 and T4 response area after methyl-TRH were significantly greater than after TRH. The methyl-TRH induced T4 response area was 1.4 times the TRH induced T4 response area. The data indicate that methyl-TRH is a more potent thyrotropin releaser than TRH. Since N3im-methyl-histidine has been found in the brain, the possibility that this methyl analogue of TRH is a physiologic thyrotropin releaser should be evaluated.

Adult↗
PubMed1976

Prolactin response to N3im-methyl-thyrotropin releasing hormone in euthyroid subjects.

The N3im-methyl analogue of thyrotropin releasing hormone (methyl-TRH) was compared with ordinary TRH as a prolactin (PRL) releaser in 32 euthyroid volunteers (20 male and 12 female, ages 17-66 years). The mean PRL response to 100 mug of methyl-TRH was greater (P less than 0.025) than the PRL response to 500 mug of TRH at 10 min and at all sampling times from 30 to 240 min after administration of the releasing factors. The mean peak PRL (at 10 min), maximum deltaPRL, and integrated PRL response area were greater (P less than 0.025) after administration of methyl-TRH than after TRH. The PRL response to methyl-TRH was greater (P less than 0.005) for the 12 women than for the 20 men in this study. The mean baseline PRL was correlated with the peak PRL (r=0.74, P less than 0.01) and the maximum deltaPRL (r=0.58, P less than 0.01) after methyl-TRH. Following administration of methyl-TRH, the peak PRL was correlated with the peak TSH (r=0.43, P less than 0.05), the maximum deltaPRL was correlated with the maximum deltaTSH (r=0.43, P less than 0.05), and integrated PRL response area was correlated with the integrated TSH response area (r=0.44, P less than 0.05). Similar correlations between PRL and TSH responses were seen after giving TRH. Age was inversely correlated with baseline PRL (r=-0.55, P less than 0.01), with maximum deltaPRL (r=-0.64, P less than 0.01), and with the PRL response area (r=0.48, P less than 0.01) after administration of methyl-TRH or TRH. Methyl-TRH did not significantly alter serum levels of growth hormone (16 subjects) and luteinizing hormone and follicle stimulating hormone (14 subjects). The results of this study indicate that methyl-TRH is a more potent prolactin releaser than TRH. Like TRH, methyl-TRH has specificity in its effects on the pituitary, releasing only TSH and PRL in normal man.

Adolescent↗
PubMed1976

Dose-response of prolactin and thyrotropin to N3im-methyl-thyrotropin releasing hormone in euthyroid men.

The synthetic N3im-methyl analogue of thyrotropin releasing hormone (methyl-TRH) was administered intravenously to 15 euthyroid men, ages 36-62, in graded doses from 6.25 mug to 500 mug in order to establish the range of response of prolactin (PRL), TSH, T3 and T4 to various doses of methyl-TRH. There was a dose-related rise in serum TSH, PRL, T3, and T4 which gave a nearly linear relationship when the integrated area of response was used as an index of response to the various doses of methyl-TRH. All 15 men had a clear elevation in TSH, PRL, T3 and T4 following the lowest dose of methyl-TRH TESTED (6.25 mug). There was considerable variability in the response to methyl-TRH among the individuals. One hundred mug of methyl-TRH gave a maximum TSH response; a 25 mug dose elicited a maximum PRL response.

Adult↗
PubMed1975

Jejunal perfusion of simple and conjugated folates in man.

The technique of human jejunal perfusion was used to study the process of digestion and absorption of conjugated folates in five healthy volunteers. The test solution of isotonic saline contained equimolar concentrations of purified [3H]pteroylmonoglutamate ([3H]PG-1) and of [14C]pteroylheptaglutamate ([14C]PG-7) which was labeled on the first glutamyl unit. Calculations were made of the luminal disappearance of each labeled folate, and degradation products of [14C]PG-7 were identified in luminal contents obtained 15 and 30 cm from the infusion site. The percentage of disappearance of [3H]PG-1 was 74.7% and of [14C]PG-7 was 52.6% (P less than 0.001)9 Column chromatography of intestinal aspirates demonstrated a spectrum of 14C-labeled folates corresponding to chain lengths from [14C]PG-1 to [14C]PG-7, with distal accumulation of derived [14C]PG-1. Intraluminal hydrolysis of [14C]PG-7 was excluded by finding the compound unchanged after in vitro incubation with intestinal juice obtained by saline perfusion or siphonage. These data indicate that there are separate rates for the luminal disappearance of PG-1 and PG-7, and show that the digestion of PG-7 requires its contact with the intestinal mucosa. The evidence suggests that progressive mucosal hydrolysis is integral to the process of PG-7 absorption in man.

Carbon Radioisotopes↗