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Biomedical subjects

P Ekman

Publications and source records attributed to P Ekman.

At least 163 records · Page 9Linked to original sources
PubMed1981

Purification of a Ca2+-activated protease from rat erythrocytes and its possible effect on pyruvate kinase in vivo.

A Ca2+-activated protease with [32P]phosphopyruvate kinase as substrate was purified to about 50% from rat erythrocytes. The purification involved chromatography on Sepharose/Sephadex gels, DEAE-cellulose and (NH4)2SO4 precipitation. The protease required 3.3 mM Ca2+ for full activity. When pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) was purified from erythrocytes incubated with [32P]phosphate it contained 0.5 mol [32P]phosphate/mol enzyme subunit. When 3.3 mM Ca2+ were added at hemolysis this incorporation decreased. The possible importance of this Ca2+-activated protease for the regulation of pyruvate kinase in erythrocytes is discussed.

Animals↗
PubMed1981

Steroid receptors in urological malignancies.

Within urological practice, three important types of cancer seem to be under endocrine influence or develop in endocrine-dependent organs: prostate cancer, hypernephroma and testicular tumors. Endocrine therapy is not used in testicular cancer, its value in renal cell carcinoma is limited, whereas it is a dominant form of therapy for prostate cancer. There seems to be a definite relation between androgen receptor content in primary prostatic carcinoma and response to hormonal manipulations. The presence of estrogen receptors is not well documented and probably the major effect of estrogen therapy is indirect, being exerted via the hypothalamo-pituitary axis. Progestin receptors are present in hyperplastic prostate as well as in prostate cancer and may indicate cases sensitive to progestin therapy. The assay method still needs considerable refinement before it can be introduced into clinical practice.

Adenocarcinoma↗
PubMed1981

Single bifid ectopic left ureter presenting clinically as a vaginal cyst.

A case of vaginal cyst formation, communicating with the bladder and with a single ectopic left ureter, is reported. It was concluded that this anomaly represented an ureter with the original relationship to the wolffian duct (Gartner's cyst). Extirpation of the cyst and reimplantation of the ectopic ureter in the bladder was performed.

Adult↗
PubMed1980

The in vitro modification of phosphorylated pyruvate kinase by a Ca2+-activated protease from rat liver.

A Ca/+-activated protease from rat liver cell sap was prepared. It was shown to act on rat liver pyruvate kinase that had been phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase, the activity being optimum at neutral pH. The modified pyruvate kinase had the same Vmax as the phosphoenzyme but showed a lower affinity for the substrate phosphoenolpyruvate. The possibility that this proteolytic attack is the step that initiates further degradation in the cell is discussed.

Animals↗
PubMed1980

Prediction of tumor response to endocrine therapy in prostatic carcinoma based on steroid receptor assay.

Measurement of estrogen receptor content in human breast cancer has become a valuable tool to predict the response of a tumor to endocrine manipulations. The aim of this study was to see whether steroid receptor assay could also be used to predict the value of endocrine therapy in human prostatic carcinoma. Biopsies from 25 primary tumors were analyzed with regard to quantity of methyltrienolone (a synthetic androgen) binding to the receptor 20 specimens were receptor-positive and 5 were receptor-negative. The correlation between receptor content and response to endocrine treatment was approximately approximately equal to 80%. The steroid receptor profiles of 5 lymph node metastases were also analyzed. 4/5 contained methyltrienolone receptors and 2/5 contained progestin receptors. 3/5 were glucocorticoid receptor-positive while all specimens were estrogen receptor-negative.

Hormones↗
PubMed1979

Steroid receptor content in human prostatic carcinoma and response to endocrine therapy.

Biopsy material from primary prostatic carcinoma from 25 patients was analyzed with regard to cytosol content of methyltrienolone (a synthetic androgen) binding sites and the receptor content has been correlated to the clinical response to endocrine therapy. A dextran-coated charcoal technique was used and binding data were calculated from Scatchard plots. In 20 of the tumors detectable levels of methyltrienolone receptor were noted. One of the receptor-positive patients died during radiation therapy before onset of hormonal treatment, and a second patient, who had a highly differentiated carcinoma, so far has not received any endocrine therapy. Of the remaining 18 patients 15 responded well to castration, treatment with estrogens, or Estracyt (approximately 80%). The biopsies from two of the three receptor-positive non-responders contained the lowest measurable receptor levels. Five specimens lacked detectable amounts of methyltrienolone receptor. Four of these patients did not respond to therapy (approximately 80%), but one was "false" negative. Our data indicate that steroid receptor analysis may become an important tool in predicting the value of endocrine therapy in human prostatic carcinoma.

Aged↗
PubMed1979

Steroid receptor content in cytosol from normal and hyperplastic human prostates.

Analyses of steroid hormone receptors were performed using a dextran-coated charcoal technique in cytosolic preparations from 40 cases of benign prostatic hyperplasia (BPH) and 10 normal human prostates. Binding data were calculated according to Scathchard. In all BPH specimens, receptors for the synthetic androgen methyltrienolone (MT) were found (mean maximum number of binding sites, 566 fmol/mg DNA; mean Kd, 0.61 nM), and 25 of 28 samples contained progestin [17 alpha, 21-dimethyl-19-nor-4.8-pregnadiene-3,20-dione (R5020)] receptors (mean maximum number of binding sites, 420 fmol/mg DNA; mean Kd, 0.39 nM). No specimen contained glucocorticoid [dexamethasone (9 alpha-fluoro-16 alpha-methyl-11 beta, 17 alpha, 21-trihydroxy-1,4-pregnadiene-3,20-dione); n = 16] or estrogen [17 beta-estradiol or 11 beta-methoxy-17 alpha-ethynyl-17 beta-estradiol (R2858); n = 26] receptors. No correlations were found between receptor content and age of the patients, weight of adenomas, or percentage of different cell types within the specimens. MT receptors were found in all normal prostates, while 5 of the specimens lacked progestin receptors. Estrogen receptors were found in 3 of the normal prostates, whereas none contained glucocorticoid receptors. The ligand specificity of the MT receptor in a normal prostate with minor amounts of progestin receptors was typical of an androgen receptor, and the ligand specificity of the R5020 receptor in a BPH specimen was typical of a progestin receptor. MT and R5020 had approximately the same affinity for the progestin receptor, whereas the relative binding affinity of R5020 for the androgen receptor was below 0.02 compared to that of MT. The androgen receptor was found to be more stable during repeated freezing and thawing than the progestin receptor.

Binding, Competitive↗
PubMed1978

Endogenous substrates of protein kinase in rat liver cell sap under different dietary conditions.

Liver cell sap from normally fed rats, rats fed with a high-carbohydrate diet and fasted rats was chromatographed on DEAE-cellulose (pH 7.0). The chromatogram from each diet group was analyzed for pyruvate kinase activity and endogenous substrates of cyclic AMP-stimulated protein kinase. The materials were pooled into five phosphorylatable fractions, in each of which phosphate incorporation at 0.1 mM and 1.0 mM [32P]ATP in the presence of cyclic AMP and protein kinase was determined. For characterization of the phosphorylatable components, thin-layer gel chromatography on Sephadex G-200 and polyacrylamide gel electrophoresis in detergent were used for determination of native and minimal molecular weights, respectively. Except for pyruvate kinase, eight components which incorporated at least 0.05 nmol of [32P]phosphate/g of liver were detected. The phosphorylation of four of them was stimulated by cyclic AMP. Their minimal molecular weights were 42000, 21000, 52000 and 49000. The component with a minimal molecular weight of 42000 seemed to have a native molecular weight of 160000. Both the 21000 and the 52000 component had a native molecular weight of about 110000-120000. The protein with a minimal molecular weight of 49000 could not be correlated with certainty to a native molecular weight. The proteins whose phosphorylation was not stimulated by cyclic AMP had minimal molecular weights of 54000, 39000, 34000 and 22000.

Animals↗
PubMed1978

Proteolytic modification of pig and rat liver pyruvate kinase type L including phosphorylatable site.

The phosphorylated or phosphate-accepting site of pyruvate kinase from pig and rat liver was removed without inactivation by incubation with subtilisin. At different time intervals the subtilisin was inactivated with phenylmethylsulfonyl fluoride and the amount of remaining phosphorylatable or phosphorylated sites of pyruvate kinase estimated by incubation with an excess of [32P]-ATP and protein kinase. It was found that to get the same rate of modification the subtilisin concentration required to modify unphosphorylated pyruvate kinase was approximately ten times higher than that used for removal of the phosphorylated site of phosphorylated site of phosphorylated enzyme. It was shown that the proteolytically-modified pyruvate kinase had an increased apparent Km for phosphoenolpyruvate without a change in V, when compared to unmodified unphosphorylated and phosphorylated pyruvate kinase. The removal of the phosphorylated site was not associated with loss of the allosteric sites for ATP and Fru-1,6-P2. The possibility that phosphorylation of the pyruvate kinase increases its degradation rate in vivo is briefly discussed.

Adenosine Triphosphate↗
PubMed1978

Correlation between clinical response to hormone therapy and steroid receptor content in prostatic cancer.

Hormonal therapy is the dominating form of treatment for prostatic carcinoma. The majority of cases (80%) are well controlled for varying times with this regimen. However, thus far there have been no adequate methods to predict in which cases hormonal therapy is of less benefit. Measurement of cancer tissue content of intracellular hormone receptors constitutes progress toward a more individualized therapy in prostatic carcinoma. In this study biopsies from 16 cancer patients were taken before therapy was given, and the specimens were analyzed with regard to content of specific methyltrienolone-binding sites. A correlation has been made between receptor content and clinical response to hormonal therapy in each case. Twelve specimens contained measurable amounts of steroid receptors. Of these, one patient died during irradiation therapy before onset of hormonal treatment. However, of the remaining 11 patients, 9 responded well to hormones (9/11 approximately 82%). The two receptor-positive nonresponders had the lowest measurable receptor levels in the series. Four specimens contained no detectable amounts of receptors. Three of these patients showed no response to therapy (3/4 = 75%) but one was "false negative." Our data indicate that steroid receptor analysis may become a valuable diagnostic tool in individualizing the therapy for prostatic cancer.

Aged↗