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Biomedical subjects

W L Miller

Publications and source records attributed to W L Miller.

At least 289 records · Page 16Linked to original sources
PubMed1979

Prostaglandin prodrugs III: Synthesis and biological properties of C9- and C15-monoesters of dinoprost (prostaglandin F2 alpha).

Methods are described for the synthesis of dinoprost C9- and C15-monoesters using protective groups. Esters at C9 were synthesized by acylation of dinoprost 11,15-bis(tetrahydropyran-2-yl)ether followed by acid-catalyzed protective group removal. Esters at C15 were synthesized by initial formation of the protected intermediate, dinoprost 9,11-n-butylboronate, followed by acylation and hydrolytic protective group removal. Many esters were active in vivo in the hamster antifertility screen. Plasma hydrolysis studies showed that the C15-esters were more readily cleaved than the C9-esters. In vivo studies in the rat showed that both the C9- and C15-esters resulted in urinary excretion of 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprosta-1,16-dioic acid in amounts comparable to those obtained after dosing with dinoprost, indicating that ester hydrolysis occurred in vivo.

Animals↗
PubMed1979

Use of recombinant DNA technology for the production of polypeptides.

DNA sequences corresponding to specific genes may be prepared by chemical synthesis, isolation of naturally occurring DNA, or reverse transcription. Such DNA may then be inserted into vectors such as plasmids or bacteriophages which carry the DNA into bacterial cells. Although significant differences exist in the basic molecular biology of eucaryotic and procaryotic organisms, these differences do not constitute absolute barriers to the expression of eucaryotic genes in bacteria. Several eucaryotic proteins, including insulin, growth hormone, ovalbumin, dihydrofolate reductase and somatostatin have been produced in bacteria. The use of chimeric microorganisms harboring recombinant DNA offers a completely new approach to the production of biologically useful polypeptides.

Base Sequence↗
PubMed1979

Responses of plasma renin activity and dopamine-beta-hydroxylase to increased intravascular volume.

Circadian variations of plasma renin activity, plasma dopamine-beta-hydroxylase, and urinary aldosterone excretion were measured in man under conditions of high- and low-sodium intake. Plasma renin activity and urinary aldosterone excretion were maximal at 8 a.m. Plasma DBH shows small, biologically insignificant circadian fluctuations. In three subjects on low-salt diets, the values were lower than those in the same subjects on high-salt diets. Expansion of intravascular volume in supine normal volunteers lowered plasma renin and DBH activity, and also resulted in a significant natriuresis. The decline in DBH activity probably reflects a decrease in its release from autonomic nerve endings and thus demonstrates in man an effect of decreasing autonomic activity.

17-Hydroxycorticosteroids↗
PubMed1979

2-(Aminomethyl)-2-decarboxyprostaglandin F2 alpha type analogs.

The 2-(aminomethyl)-2-decarboxy analogs of prostaglandin F2 alpha (PGF2 alpha), (15S)-15-methyl-PGF2 alpha, 16-phenoxy-omega-tetranor-PGF2 alpha and 16,16-dimethyl-PGF2 alpha were synthesized. The amino analogs closely resemble the parent PGF2 alpha compounds as antifertility agents in the hamster.

Abortifacient Agents↗
PubMed1979

Transmural distribution of myocardial adenosine content during coronary constriction.

The transmural distribution of tissue adenosine content was determined in samples of the left ventricle of anesthetized open-chest dogs. Transmural tissue samples were obtained and quickly freeze-clamped during either normal coronary perfusion or partial constriction of the inflow tubing to the left common coronary artery. Inner, middle, and outer segments of the samples were assayed for adenosine, inosine, ATP, creatine phosphate, and lactate. In control experiments, there were no significant differences among the tissue contents of the substances in the three segments. However, during a 50.2 +/- 4.7% reduction of coronary inflow, adenosine content of inner, middle, and outer segments was 0.41 +/- 0.007, 0.030 +/- 0.006, and 0.016 +/- 0.003 nmol/mg protein, respectively. Outer segment content was significantly less than either middle or inner content. Lactate distribution was similar to that of adenosine, whereas ATP and creatine phosphate were lowest in the inner segment. Increases of the inner/outer adenosine ratio occurred when the coronary-ventricular pressure index was lower than 1.2. Thus, selective underperfusion of the subendocardium during reduced coronary inflow can result in greater accumulation of adenosine in that region.

Adenosine↗
PubMed1979

An infant with Cushing's disease due to an adrenocorticotropin-producing pituitary adenoma.

An 8-month old male with Cushing's disease is presented; his clinical presentation and appearance were typical of infants with glucocorticoid excess. Concentrations of cortisol, 17-hydroxyprogesterone, and adrenal androgens were strikingly elevated. High doses of dexamethasone did not suppress the excretion of urinary free cortisol or 17-hydroxycorticoids, and administration of ACTH elicited no further rise in plasma cortisol. Responses of LH, FSH, and PRL to iv LRF and TRF were appropriate for age, but neither TSH nor ACTH rose significantly. Plasma ACTH values were elevated to 700 pg/ml. An intracranial mass lesion superior and anterior to the sella turcica was demonstrated by computerized axial tomography and angiography. An inoperable pituitary adenoma was a massive surrounding fibroblastic reaction was found at craniotomy. The pathological diagnosis of an ACTH-producing pituitary adenoma was confirmed by immunohistochemistry and by the in vitro secretion of ACTH by cells cultured from the tumor.

17-Hydroxycorticosteroids↗
PubMed1979

Translation of messenger RNA from fetal and adult mouse kidney.

Polyadenylated mRNA was prepared from fetal, adult, and regenerating adult mouse kidneys. The polyadenylated portion is 2% of total RNA in the fetus, falls abruptly to 1% after birth, and returns to about 2% in the adult. In vitro translation of these mRNA's showed great similarities between 17 and 20 day fetal samples and between the normal and regenerating adult samples, but few similarities between the fetal and adult samples. The data do not support the hypothesis that renal growth following contralateral nephrectomy may entail the de-repression of genes active in the fetus but not active in the normal adult.

Aging↗
PubMed1978

Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog.

Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.

Animals↗
PubMed1978

Adenosine production in the ischemic kidney.

We conducted experiments to determine (1) tissue, blood, and urine levels of adenosine produced by the ischemic kidney under conditions of renal artery occlusion, and (2) the site(s) of production and release of adenosine by the kidney. Concentrations of adenosine, inosine, and hypoxanthine in the dog urine were found to increase after 2 minutes of renal artery occlusion as were concentrations of these metabolites in renal tissue after 10 minutes of renal artery occlusion. Renal venous plasma levels of inosine and hypoxanthine also were elevated after 3 minutes of arterial occlusion. In modified stop-flow experiments, adenosine appeared in the urine in a peak that corresponded most closely with proximal tubule fluid. 5'-Nucleotidase, the enzyme which catalyzes the dephosphorylation of 5'-AMP or 5'-IMP to adenosine or inosine, respectively, was found to be located primarily on the external membranes and mitochondria of proximal tubule cells, but not in distal tubule or collecting duct cells. Since adenosine has been demonstrated to elicit renal vasoconstriction and is produced by the ischemic kidney, it is suggested that adenosine may be involved in the mediation of postocclusion renal ischemia.

Adenosine↗
PubMed1977

Estrogen regulation of follicle stimulating hormone in cell cultures of sheep pituitaries.

Cell cultures of ovine pituitaries were maintained for up to 3 weeks. A specific double antibody radioimmunoassay was used to measure FSH in the media and cells. The rate of FSH synthesis increased in the cultures during the first 4-6 days to a level of approximately 50 ng/day/106 cells, generally remained constant for 2 weeks and then decreased. The FSH produced in vitro migrated similarly to highly purified ovine FSH on P-60 polyacrylamide gel filtration columns and had a biological potency essentially identical to that of the highly purified FSH standard. Addition of 17beta-estradiol (E2) at 10-9M on days 2 or 6 incubation decreased FSH synthesis greater than 95% within 30 h. Time-course analysis revealed that the effect of E2 can be observed as early as 6 h after treatment. FSH synthesis resumed after removal of E2 and reached control levels within 6 days. The lowest effective dose of E2 was 10-11M; E2 at 5 X 10-11M maintained FSH production at approximately 50% of the control levels. Diethylstilbestrol was as active estriol was 1/10th as active and 17alpha-estradiol was 1/100th as active as E2. Progesterone (P), 5alpha-pregnane-3,20-dione (5alphaDHP), 20alpha-hydroxy-pregn-4-en-3-one(20alpha-OHP), testosterone, 5alpha-dihydrotestosterone and corticosterone had no effect on FSH levels. These findings suggest that estrogen is capable of playing a major role in FSH synthesis and release by action directly at the pituitary level.

Animals↗
PubMed1977

Estrogen action in vitro: regulation of thyroid stimulating and other pituitary hormones in cell cultures.

Primary cell cultures of ovine pituitaries can maintain production of thyroid stimulating hormone (TSH) for as long as 24 days. These cultures responded in a normal fashion to thyroxine by decreasing TSH secretion. Addition of thyrotropin releasing hormone increased TSH secretion. Physiologic levels of estradiol-17 beta (10(-11)-10(-9)M) produced a five-fold increase in secretion of TSH and a two-fold increase in intracellular TSH concentration in cell cultures. Common estrogens, but not common progestins, androgens and glucocorticoids affected TSH production. Markedly different effects of estrogen in the pituitary on follicle stimulating, luteinizing and thyroid stimulating hormones and prolactin are discussed in terms of current models of estrogen action.

Animals↗
PubMed1976

Relative biological activity of certain prostaglandins and their enantiomers.

A series of mirror image (ent) forms of prostaglandins F2 and E2 have been compared for potency in a hamster antifertility test. In the PGF2 series, ent-compounds surveyed had less potency than corresponding natural structures. For the PGE2 series, 11alpha-(15S)-ent-PGE2 methyl ester was 10-fold more potent than PGE2. Altering the C-9 hydroxy configuration in the PGF2 series from the natural alpha to beta decreased potency dramatically for compounds tested.

Animals↗
PubMed1975

Interactions between prostaglandin analogues and a receptor in bovine Corpora lutea. Correlation of dissociation constants with luteolytic potencies in hamsters.

The dissociation constants for the interactions between some prostaglandin analogues and a prostaglandin F2 receptor in bovine corpora lutea were determined. These values were compared to the antifertility potencies of these compounds in hamsters and the rates of metabolism by 15-hydro-syprostaglandin dehydrogenase. The most active analogues with regard to both affinity for the receptor and luteolytic potency were 17-phenyl-18, 19, 20-trinorprostaglandin F2alpha and 15-methylprostaglandin F2alpha. The alkyl side chain of prostaglandins could be modified considerably without altering the affinity for the receptor. In this way metabolism by 15-hydroxyprostaglandin dehydrogenase could be blocked. Some of these compounds -ad greatly increased luteolytic effects. Substitution of a phenyl group for the 3 terminal carbon units of the alkyl side chain of prostaglandins increased both the affinity for the receptor and the luteolytic activity in vivo. 7-oxa-13-prostynoic acid, an antagonist of the luteolytic effect of prostaglandin F2alpha in vivo was a weak competitive inhibitor of the interation between prostaglandin F2alpha and the receptor.

Animals↗