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Biomedical subjects

M Edmonds

Publications and source records attributed to M Edmonds.

At least 37 records · Page 2Linked to original sources

Poly(uridylic acid) sequences in messenger ribonucleic acid of HeLa cells.

The poly(uridylic acid [poly(U)] sequences of 30 to 40 nucleotides found in the heterogeneous nuclear ribonucleic acid (RNA) Of HeLa cells are also present in the poly(adenylic acid) [poly(A)] containing messenger RNA (mRNA) of these cells. Twenty-five percent of the total poly(U) sequences in the cell are found in the cytoplasm after HeLa cells have been labeled for 2.5 h with 32P. This value is close to 40% if only poly(A) containing RNA molecules of the cell are considered. The distribution of poly(U) sequences parallels that of poly(A) sequences in different size classes of cytoplasmic messenger RNA. From the concentrations and lengths of the two sequences it can be estimated that about 20% of the poly(A) containing mRNA molecules could contain one poly(U) sequence. Several lines of evidence have been developed to rule out poly(U) containing heterogeneous nuclear RNA (HnRNA) as the source of the poly(U) sequences in cytoplasm. Poly(U) sequences are also found in RNA molecules of the nucleus and cytoplasm which do not contain poly(A). Although poly(U) sequences are most abundant in nuclear RNA species lacking poly(A), they are well represented in a class of RNA molecules in cytoplasm which lack poly(A), but which otherwise resemble the polysomal mRNA of HeLa cells.

Base Sequence

Short-loop feedback control of luteinizing hormone in the rabbit.

A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration.

Animals

Secretion of alpha and beta subunits of TSH by the anterior pituitary.

We have attempted to determine whether blood concentrations of the alpha chains of TSH arise by direct pituitary secretion of alpha chain or by degradation of the intact hormone after secretion. Highly purified human TSH was administered by infusion to euthyroid volunteers; blood TSH concentrations were raised to 36 muu/ml. After TSH infusion, circulating blood alpha chain concentrations did not change. The same volunteers received an infusion of TRH which stimulated pituitary secretion of TSH, raising blood concentrations to 15 muu/ml in one series of subjects and to 23 muu/ml in a second series. After TRH, blood concentrations of alpha chain increased from undetectable to over 400 pg/ml. We conclude that alpha subunits of TSH are directly secreted by the pituitary gland and are not formed by degradation of intact TSH in the peripheral circulation.

Humans

Secretion of alpha subunits of luteinizing hormone (LH) by the anterior pituitary.

Free alpha subunit chains of the glycopeptide pituitary hormones have been found in the sera of normal subjects and postmenopausal women. To ascertain whether the alpha subunit of LH is directly secreted by the pituitary or formed as a result of degradation of intact LY in the periphery, alpha subunits and intact LH were measured by radioimmunoassay in human volunteers after LRF stimulation and purified LH infusion. In 4 subjects a loading dose of 90 IU, followed by the infusion of 22.5 IJ of purified human LH over 30 min, produced peak serum LH levels of 41 mIU/ml but no change in alpha subunit levels of 35 IU of purified human LH to an additional 4 subjects, produced peak LH levels of 8* mIU/ml, but again, no change in alpha subunits. In the same two groups of subjects 100 mug of LRF produced peak LH levels of 25 mIU/ml and 75 mIU/ml, respectively, with significant alpha subunit elevations at 20 min of 1.7 ng/ml and 2.7 ng/ml, respectively. In separate groups of men LRF was administered over a wide dose range of 1 to 3,000 mug and LH and the alpha subunit measured. A dose-response curve existed over the entire LRF dose range for blood LH; no minimum or maximum plateaus were observed over the range studied. However, the alpha chain response appeared to reach a maximal plateau at a dose of 100 mug of LRF. The results are compativle with the hypothesis that the alpha subunits appearing in the peripheral circulation in response to LRF are due to secretion by the anterior pituitary and not due to peripheral degradation of intact secreted LH.

Dose-Response Relationship, Drug

Differential metabolism of large and small poly(A) sequences in the heterogeneous nuclear RNA of HeLa cells.

The heterogeneous RNA of the HeLa cell nucleus contains short internal poly(A) sequences which, in contrast to the longer poly(A) sequences at the 3' ends, are not found in messenger RNA of the cytoplasm. A distinct origin for each of these homologous sequences is evident when the effects of actinomycin D and 3'-deoxyadenosine on their biosynthesis are compared. The shorter poly(A) appears to be transcribed, while the longer one does not. A kinetic analysis of the metabolism of each type of poly(A) sequence within different size classes of HnRNA after treatment of the cells with 3'-deoxyadenosine reveals distinctive distribution and metabolism of these sequences and also provides insight into mechanisms proposed for the generation of messenger RNA from these large RNA molecules in the nucleus.

Adenine Nucleotides