Biomedical subjects

M M Phillips

Publications and source records attributed to M M Phillips.

8 recordsLinked to original sources

PubMed1984

Binding of the rat liver 7-8 S dexamethasone receptor to deoxyribonucleic acid.

The 7-8 S form of the [3H]dexamethasone (9 alpha-fluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3, 20-dione) receptor from rat liver cytosol can be converted to the 3-4 S form by RNase treatment or high salt, suggesting a salt-sensitive association between the receptor protein and RNA. In DNA-cellulose column assays, the gradient-purified 3-4 S form bound DNA more efficiently than the 7-8 S form, though the 7-8 S form was also capable of binding to DNA-cellulose to a significant extent. Activated 7-8 S dexamethasone receptor could be released from its association with soluble DNA by treatment with DNase I. Sucrose gradient analysis showed that the released receptor sedimented as the 7-8 S form and was sensitive to RNase treatment, which induced a conversion to the 3-4 S form. Activated RNase-generated 3-4 S receptor again displayed a higher degree of binding to soluble DNA and was recovered in the 3-4 S form following DNase extraction. The fact that the 3-4 S form bound immobilized or soluble DNA more efficiently suggests that the associated RNA of the 7-8 S form interferes directly or indirectly with the receptor association with DNA. The observation that the receptor binds to DNA in its 7-8 S form suggests that the receptor complex is capable of binding RNA and DNA concurrently.

Animals↗

PubMed1984

Analysis of androgen-sensitivity in rat prostate X mouse kidney cell hybrids.

Variant androgen-sensitive cell lines were produced by fusing freshly isolated epithelial cells from the rat ventral prostate with a line of murine renal tumor (RAG) cells. The properties of the cloned lines of the prostate X RAG hybrids can be summarized as follows: (1) the modal chromosome number of the hybrid cell lines ranged from 68 to 176; (2) the cells had doubling times of 7.6-49.5 h; and (3) epitheloid, ameboid and intermediate morphologies were observed among the various lines. The proliferative response of various hybrid lines to treatment with 10 nM 5 alpha-dihydrotestosterone was used to classify the hybrids as either very sensitive (greater than 40% reduction in cell doubling time), sensitive (greater than 10% reduction in doubling time) to androgens, or insensitive (less than 10% reduction in doubling time) to androgens. There was no direct relationship between the androgen-sensitivity of the cells and their androgen receptor content, suggesting that these variant cell lines may be useful for the study of the genetic factors involved in cellular responses to androgens.

Animals↗

PubMed1984

Steroid metabolism and binding activity in a murine renal tumor cell line.

The purpose of this study was to partially characterize the steroid binding activity of murine renal tumor cells in continuous culture. The steroid receptor content of a cloned renal tumor cell line (RAG) and a subline RAG-2 was examined by sucrose gradient analysis, hydroxylapatite and dextran-coated charcoal methods. The RAG cells lacked estrogen- and progestin-binding activity, whereas specific 5 alpha-dihydrotestosterone (DHT) and dexamethasone (Dx) binding activities were detected as 8S peaks on low salt gradients. The specificity of DHT binding was examined by sucrose gradient analysis: DHT, R1881 and ORG2058 all completely inhibited [3H]DHT binding whereas diethylstilbestrol and Dx were ineffective. The androgen receptor content of the RAG cells was approx. 15 fmol/mg cytosol protein by the hydroxylapatite-filter assay, with an estimated Kd for methyltrienolone (R1881) of 5 nM at 0 degrees C. Scatchard analysis of [3H]Dx binding by RAG cytosol showed a Kd of 6 nM for Dx and 44 nM for corticosterone at 0 degrees C. Glucocorticoid receptor levels were estimated to be 182 fmol/mg cytosol protein by dextran-coated charcoal assay. Metabolism of [3H]testosterone and [3H]DHT by RAG cells was examined 1, 4 and 6 h after exposure to labeled hormone. Radioactive DHT was the primary intracellular metabolite recovered after exposure to [3H]testosterone. There was little conversion of DHT to androstanediol.

Animals↗

PubMed1983

The effects of ribonuclease on rat liver dexamethasone receptor: increased affinity for deoxyribonucleic acid and altered sedimentation profile.

The ability of the dexamethasone (9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione)-receptor complex to bind to DNA-cellulose is stimulated by RNase treatment of the activated receptor. Both RNase A and RNase T1 can induce the stimulation. The enhancement of the DNA binding ability occurs concomitantly with an alteration of the sedimentation profile of the dexamethasone-receptor complex from the 7-8S form to the 3-4S form in low salt sucrose gradients. If RNase treatment occurs in the presence of sodium molybdate, both the increase in DNA binding ability and the alteration in sedimentation profile fail to occur. Treatment of the receptor with high salt suggests that the 3-4S form can reversibly combine with a factor in a salt-sensitive association. These experiments indicate that the 7-8S form of the dexamethasone-receptor complex is associated with a RNA molecule(s) that can be removed by RNase treatment or salt dissociation, and that this RNA inhibits the binding of the receptor to DNA.

Adrenalectomy↗

PubMed1977

Adrenocorticosteroid therapy in alcoholic hepatitis. A prospective, double-blind randomized study.

In a prospective, randomized, double-blind study of prednisolone therapy of acute alcoholic hepatitis, 39% of the total group of 28 patients died. Mortality and cumulative survival were similar in steroid- and placebo-treated patients. After 14 days of therapy, the serum albumin concentration and white blood count were significantly higher in the steroid group, but all other parameters were similar. An increased risk of fungal infection appeared to be associated with steroid therapy.

Acute Disease↗

PubMed1975

Portacaval anastomosis and peptic ulcer: a nonassociation.

The incidence of peptic ulcer is increased in cirrhosis and is widely believed to be even greater in cirrhotic patients with portacaval anastomosis (PCA). Two prospective, controlled investigations of prophylactic PCA were evaluated to compare the frequency of peptic ulcer in two groups of cirrhotic patients with similar clinical and laboratory manifestations of cirrhosis randomly selected to be an unoperated Control Group (60 patients) or to have PCA (Shunt Group, 48 patients). In addition, nonrandomized groups of cirrhotic patients, 77 of whom were excluded from the randomized study and 44 of whom had therapeutic PCA, were studied. A diagnosis of chronic peptic ulcer was based on the demonstration of an ulcer crater by X-ray, endoscopy, surgery, or autopsy. Prior to inclusion in these studies, approximately 10% of patients had had peptic ulcer. After inclusion, during a mean follow-up period of 45 months, 12% of both the Control and Shunt Groups developed peptic ulcers. The frequency of complications of peptic ulcer, of recurrence of peptic ulcer, or of acute or symptomatic (unproved) ulcer were similar in both groups. Ulcers tended to develop later in shunted than in unshunted patients. Similar data were obtained from three of four other controlled investigations of PCA. This investigation does not find an increased occurrence of peptic ulcer after PCA. The frequency of ulcer in cirrhosis appears to increase with the duration of the disease independent of the presence or absence of PCA.

Autopsy↗

PubMed1975

Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial.

Intraarterial vasopressin has been reported to be effective in the treatment of massive upper gastrointestinal hemorrhage. A prospective, controlled clinical trial comparing conventional treatment with conventional therapy plus intraarterial vasopressin was undertaken. Sixty episodes of upper gastrointestinal hemorrhage were evaluated during a 40-month period; 32 received conventional and 28 conventional plus vasopressin therapy. The two groups of patients were similar in type and severity of their bleeding lesions and in their underlying diseases. Vasopressin was more effective in controlling hemorrhage from nonvariceal lesions (P less than 0.05) and from varices (P less than 0.01) than conventional therapy. Transfusion requirements were significantly reduced in those patients who received vasopressin. Paradoxically, survival was not affected by vasopressin administration. The failure of cessation of hemorrhage to improve survival is thought to be due to the degree of advancement of the underlying disease, to the torrential nature of the hemorrhage, to the frequency of recurrent hemorrhage, and to the use of intraarterial vasopressin in some patients in the conventional treatment group in whom conventional therapy had failed.

Adult↗

PubMed1971

Dysphagia.

Explore the source record for details and available documents.

Deglutition Disorders↗