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Biomedical subjects

A Pousette

Publications and source records attributed to A Pousette.

At least 73 records · Page 4Linked to original sources

PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: relation to hormone sensitivity and to cytological grading.

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.

Acid Phosphatase↗

A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy.

The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.

Administration, Oral↗

Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens.

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.

Aged↗

Estrogen therapy and liver function--metabolic effects of oral and parenteral administration.

Oral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver-derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.

Administration, Oral↗

Androgens during different modes of endocrine treatment of prostatic cancer.

Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone (17OHP), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS) and cortisol were measured before and after 6 months of treatment in prostatic cancer patients treated by orchidectomy (ORX) or with oral + parenteral estrogens (OE), single parenteral estrogens (PE; 160 or 320 mg polyestradiol phosphate i.m. every fourth week), estramustine phosphate (ECYT) or LHRH agonist without (LHRH) or with (LHRH-F) flutamide. Castration values of T and 170HP were reached in all types of treatment (PE at the higher dose). A-4 levels were suppressed by all treatment regimens except ECYT; DHA by OE and LHRH-F and DHAS by ORX, OE and LHRH-F. The most pronounced suppression was found in the LHRH-F group. Cortisol levels were markedly increased by OE and ECYT. The observed effects on the adrenal androgens A4, DHA and DHAS and on cortisol probably reflect different degrees of liver interaction rather than interaction with adrenocortical steroid synthesis.

Aged↗

Serum factors stimulate the motility of human spermatozoa.

Motile human sperm were collected from a Percoll gradient and the effects on sperm motility of human serum, various serum fractions, follicular fluid and seminal plasma were assessed. In culture medium alone (RPMI-1640) sperm motility was lost after about 5 h. The addition of male blood serum both enhanced sperm motility and prolonged viability very significantly. Albumin, seminal plasma and follicular fluid all stimulated sperm motility but to a much lesser extent than did blood serum. No difference was noted between male serum or female serum which had been collected during the follicular or luteal phases of hormone-stimulated cycles and which contained high levels of oestradiol. Serum fractions obtained by separation on Sephacryl S-300 column were tested for their ability to enhance sperm motility. The most pronounced effect, much superior to that achieved by the albumin fraction, was obtained by a fraction with a molecular weight of around 200 kD. In conclusion, certain factors in human serum, which are different from albumin, strongly support sperm motility. The high serum concentrations of oestradiol resulting from hormone stimulation for in-vitro fertilization do not invalidate the use of serum from the same patient during sperm preparation, or in the medium used for ovum insemination and culture.

Blood Physiological Phenomena↗

Scheduled intermittent periods of in vitro fertilization treatments.

Organization and results of an in vitro fertilization program at the Huddinge University Hospital are given from its beginning in August 1985: 6 months in advance a scheme is scheduled with 2 weeks open for treatment followed by free intervals of 3-4 weeks. Follicular development is stimulated with clomiphene citrate and hMG, and assessed by analyses of estradiol and LH in serum combined with ultrasound examinations. Following the administration of hCG, eggs are collected by transvesical aspiration guided by ultrasound. The ova are inseminated with about 50,000 motile spermatozoa, and cultured for 48 h. Up to four eggs are transferred transcervically to the uterine cavity. 158 egg pickups have been performed (August 1985 to December 1987) in 106 patients resulting in fourteen intrauterine and two ectopic pregnancies, biochemical pregnancies not counted. This protocol has restricted routine work load allowing these treatments to be part of the clinical routine. It has also allowed the application of research programs and thus optimized limited resources.

Adult↗

Pancreas-specific protein. New serum marker for graft rejection in pancreas-transplant recipients.

A radioimmunoassay for a novel human pancreatic protein (pancreas-specific protein, PASP) has been developed. We studied the possibility that serum PASP levels reflect pancreas-graft rejections in human pancreas-transplant recipients. Ten patients subjected to combined pancreas-kidney transplantation and 4 patients subjected to pancreas transplantation alone were studied. Twelve kidney recipients served as control subjects. On several occasions, PASP levels were elevated at kidney rejections in patients with combined pancreas-kidney grafts and then decreased after antirejection therapy, although no other indications for concomitant pancreas-graft rejection were at hand. In the recipients of pancreas grafts alone, PASP levels increased before or at the same time as graft rejections were indicated by current methods. In two cases of chronic graft rejection, PASP rose to high levels long before hyperglycemia occurred. In the control group of kidney-graft recipients, PASP levels were stable and were not affected by high serum creatinine levels, kidney-rejection episodes, or antirejection therapy. This study indicates that PASP may be a good serum marker for pancreas-graft rejection.

Adult↗

A novel assay for pancreatic cellular damage: III. Use of a pancreas-specific protein as a marker of pancreatic graft dysfunction in humans.

Pancreas-specific protein (PASP) is a recently isolated and partially characterized major protein in the human pancreas. It has not been described previously. Serum levels of PASP and amylase were analyzed in 21 patients subjected to combined renal and segmental pancreatic transplantation with both organs obtained from the same donor and in eight kidney transplant patients. In the pancreas transplant patients, PASP and amylase levels were elevated in episodes of graft pancreatitis. With chronic graft rejection, PASP rose to high levels long before other indications. In episodes of renal rejection, the levels of PASP, but not always of amylase, were elevated on several occasions. They decreased after antirejection therapy. This may indicate accompanying pancreatic graft rejection. PASP and amylase levels were stable in kidney transplant patients and were not affected by serum creatinine levels, renal rejection, or antirejection therapy. The results support earlier observations that renal rejection in combined pancreas and renal transplant patients may or may not be accompanied by a rejection process in the pancreatic graft. PASP may be the means by which to tell when the pancreatic graft is involved.

Adult↗

Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate.

Thirty-eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections--160 mg, 240 mg, and 320 mg--in this nonrandomized study. In contrast to studies with oral estrogens, there have been no cardiovascular complications at a mean follow-up of 12.9 +/- 0.7 months (SEM). Twenty-nine of the 38 patients (76%) have responded to therapy.

Aged↗

Growth inhibiting effect of estramustine on two prostatic carcinoma cell lines, LNCaP and LNCaP-r.

The effect of estramustine (EM), estradiol-17 beta (E2) or 5 alpha-dihydrotestosterone (DHT) on the growth of two human prostatic carcinoma cell lines, LNCaP and LNCaP-r was investigated. The hormone resistant subline LNCaP-r was derived in our laboratory, from the hormone sensitive LNCaP cell line. E2, 10(-8) or 10(-5) M inhibited the growth of the LNCaP cells, but did not affect the LNCaP-r. DHT, 10(-8) M, had a stabilizing effect at the stationary phase on the growth of the LNCaP cells whereas at higher concentrations, 10(-5) M, the growth rate was decreased. The LNCaP-r cell line was previously reported to be unaffected by DHT. EM inhibited the growth of both cell lines but LNCaP was more sensitive than LNCaP-r. E2 and DHT modulated the effect of EM. When treated with 10(-7) M EM, addition of E2 or DHT (10(-7)-10(-5) M) further inhibited the growth. When EM was used at a higher concentration (10(-5) M), the enhanced effect of growth inhibition by hormone addition was lost. Based on these results it is suggested that the presence of endogenous hormones, or estrogens released from EM on hydrolysis, may play a contributory role in the cytotoxicity of estramustine.

Cell Division↗

The estrogen binding protein in human pancreas: concentrations in subcellular fractions of normal pancreatic tissue, in duodenal juice during pancreatic stimulation and in peripheral serum in normal and pathological conditions.

The steroid binding properties of the human pancreatic estrogen binding protein (hEBP) in cytosol were studied by equilibrium dialysis. A high ligand specificity of the protein was revealed. hEBP in cytosol binds unconjugated steroid estrogens with a medium affinity (Kd = 10(-7) M) but does not bind conjugated estrogens or unconjugated androgens, gestagens, glucocorticoids or cholesterol. Quantitation of hEBP by radioimmunoassay in subcellular fractions of human pancreatic tissue indicated that the protein is translocated into different subcellular compartments. Duodenal juice taken from patients following stimulation of pancreatic secretion by food ingestion (Lund's test) showed high hEBP concentrations, and the levels of hEBP changed concomitantly with the levels of pancreatic isoamylase, indicating that hEBP secretion was stimulated by food ingestion. The levels of hEBP in peripheral serum from healthy subjects showed no sex difference, but were positively correlated to age. Highly elevated (10-20-fold) hEBP levels were found in serum from patients with acute pancreatitis, while normal serum hEBP values were found in other abdominal diseases. It is speculated that hEBP might have a specific role in the transport of estrogens from the peripheral circulation via the pancreas to the duodenum. The elevated hEBP levels in patients with acute pancreatitis indicate that this protein may be used as a marker of cellular damage in the pancreas.

Carrier Proteins↗

Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex.

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20-87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20-84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.

Adult↗

A novel serum assay for pancreatic cellular damage. II. High tissue specificity of a pancreatic protein.

A previously unknown major protein in human pancreatic cytosol has been purified and partly characterized. The protein, designated pancreas specific protein (PASP), has a molecular weight of 44,500 and a pI of 6.9. A two-dimensional gel separation technique revealed the protein to be specific for normal pancreatic tissue. Antibodies against PASP were raised in rabbits and a radioimmunoassay was developed for the quantitation of this protein. The following concentrations of PASP (mg/kg wet weight) were found in human tissues: normal pancreas 100-1,000; pancreatic carcinoma 0.1-20; prostate 0.5-5; and 13 other tissues less than 0.5. The levels of PASP in peripheral serum were less than 0.1 mg/L in normal subjects, 0.7-3 mg/L in cases of acute pancreatitis, and less than 0.1 mg/L in cases of pancreatic carcinoma, prostatic diseases, and other abdominal diseases investigated. The high tissue specificity and the specific elevation of serum PASP levels in acute pancreatitis may indicate a use of this protein as a marker of this pancreatic condition.

Biomarkers↗

Hormone levels in male ice hockey players during a 26-hour cup tournament.

Pituitary, adrenal and testicular hormones and steroid-binding proteins were analysed in 15 active ice hockey players and in 16 spectators, matched for physical fitness, during a 26-h cup tournament including three matches. Diurnal variations were noted for all compounds except FSH and SHBG. The levels of cortisol, dehydroepiandrosterone (DHA), 4-androstene-3, 17-dione (A-4) and prolactin increased in players but not in spectators following the matches played in the afternoons, but not following the match played in the morning. Albumin and DHA sulphate (DHAS) levels increased in players following all three matches and SHBG levels increased slightly in players following the afternoon matches, all probably due to haemoconcentration. DHAS and albumin showed simultaneous diurnal variations with a nadir in the morning. 17 alpha-hydroxyprogesterone (17-OHP) and total and non-SHBG-bound testosterone showed similar diurnal patterns in spectators, with maximum levels in the morning. Levels of 17-OHP were largely unaffected by physical stress, while the morning maximum for total and non-SHBG-bound testosterone was completely abolished in players. Minor or insignificant changes were noted for LH and FSH. While the changes in unconjugated adrenal steroids (cortisol, DHA and A-4) reflect changes in acute ACTH stimulation, changes in albumin binding may be more important for the short-term variations in levels of DHAS. The influence of physical stress upon the pattern of testosterone may be mediated mainly by inhibition of testicular steroidogenesis by elevated cortisol and/or prolactin levels, rather than by decreased gonadotrophic stimulation or by alterations in binding to SHBG.

17-alpha-Hydroxyprogesterone↗

Ciclosporin-associated hypertrichosis is not related to sex hormone levels following renal transplantation.

To study a possible relationship between ciclosporin-induced hypertrichosis and sex hormone pattern, the hair growth in different areas of the body was graded and hormone levels were assayed before and up to 6 months after kidney transplantation. Increased hair growth was observed in 100% (23/23) of the patients in skin areas connected with androgen action and in 78% of the patients in androgen-insensitive areas. After renal transplantation the pituitary, testicular and adrenal hormone levels normalized. The posttransplantation levels of these hormones would not explain the observation of increased hairgrowth. Thus, ciclosporin induces hypertrichosis via a mechanism independent of sex hormones.

Adult↗

Novel assay for pancreatic cellular damage: 1. Characterization of protein profiles in human pancreatic cytosol and purification and characterization of a pancreatic specific protein.

The protein patterns of cytosols from normal human pancreas and pancreatic carcinoma were studied by a two-dimensional separation technique using high-performance liquid chromatography followed by isoelectric focusing on polyacrylamide gels and visualization of the focused proteins by Coomassie Blue staining. Almost identical protein patterns were obtained for 20 different specimens from normal pancreas, whereas quite different protein patterns were found in 12 samples of pancreatic carcinoma. A major protein in normal pancreatic cytosol, not identical to any macromolecule previously tested as a marker for pancreatic function, was selected for further studies. The protein was not found in specimens of pancreatic carcinoma. It was purified by a single step chromatofocusing procedure, focused at pH 6.9, and moved as one single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 44,500 daltons. Total amino acid analysis revealed a high concentration of glutamic acid, leucine, and lysine. The purified protein had no amylase activity or lipase immunoactivity. It constituted approximately 2% of the total normal pancreatic cytosol protein. Later immunological studies have shown the protein to be highly specific for normal human pancreas, indicating a possible future use as a marker for pancreatic cell damage.

Adenocarcinoma↗

Single drug polyestradiol phosphate therapy in prostatic cancer.

Serum concentrations of testosterone (T) and estradiol-17 beta (E2) were analyzed in prostatic cancer patients treated with 160, 240, or 320 mg polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period. Estrogen effects on the liver were studied by analyzing serum levels of sex hormone binding globulin (SHBG) in the 320 mg group and compared with values obtained in patients treated with 80 mg PEP i.m. every fourth week + oral ethinylestradiol (EE2) 150 micrograms daily, or by orchidectomy. Orchidectomy levels of T were reached within 3 weeks in the 320 and 3 months in the 240 mg group. In the 160 mg group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1,300-2,500 pmol/L at 6 months. At 6 months, SHBG levels had increased to 617% of pretreatment values in the oral EE2 group, to 166% in the 320 mg group, and were unaffected by orchidectomy. No cardiovascular side effects occurred during single-drug PEP treatment.

Aged↗