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P Vihko

Publications and source records attributed to P Vihko.

126 records · Page 7Linked to original sources
PubMed1981

Androgens and prostate-specific acid phosphatase in whole tissue and in separated epithelium from human benign prostatic hypertrophic glands.

The concentrations of prostate-specific acid phosphatase (PAP), testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 alpha-androstane-3 alpha, 17 beta-diol, androstenedione, 5 alpha-androstanedione, and androsterone were measured by specific radioimmunoassays in whole pieces and in separated epithelium from human benign prostatic hypertrophic (BPH) tissues. Significant correlations were noted between the concentrations of PAP and 5 alpha-DHT, and PAP and 5 alpha-androstane-3 alpha, 17 beta-diol in the epithelium, and between PAP and androstenedione, and PAP and testosterone PAP is androgen dependent, particularly as regards 5 alpha-DHT, whereas 5 alpha-androstane-3 alpha, 17 beta-diol may operate after conversion to 5 alpha-DHT. There is no obvious explanation for the correlations noted in whole tissue, but is suggested that circulating androgens, representing the androgen source for the prostate, primarily determine the production of PAP. The majority of the PAP in BPH tissues is located extracellularly.

Acid Phosphatase↗
PubMed1981

Radioimmunoassay of human prostate-specific acid phosphatase. A sensitive and specific assay for semen detection in forensic medicine.

Human prostate-specific acid phosphatase was measured by a rapid and sensitive radioimmunoassay in samples which originated from investigations of suspected sexual assaults and in which microscopic examination did not show sperm cells. Of the 12 samples, Ouchterlony double immunodiffusion showed the presence of spermatic fluid in three samples, whereas radioimmunoassay detected an additional seven spermatic fluid-positive ones. It is also shown that the procedure is sensitive enough for forensic medical purposes to detect semen in highly diluted postcoital vaginal fluid, and no cross-reactivity with nonseminal samples tested was observed.

Acid Phosphatase↗
PubMed1981

Clomiphene citrate administration to normogonadotropic subfertile men: blood hormone changes and activation of acid phosphatase in seminal fluid.

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2-10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly unchanged. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn++ and Mg++.

Acid Phosphatase↗
PubMed1981

Transient high serum prostate-specific acid phosphatase measured by radioimmunoassay in prostatic infarction.

Extremely high concentration, 172-hold the upper limit of reference range, of serum prostate-specific acid phosphatase was measured by radioimmunoassay in a patient subsequently shown to have prostatic infarction associated with prostatic hyperplasia. Following retropubic prostatectomy, the serum concentration of acid phosphatase returned to normal range. This finding shows that even grossly elevated levels of prostatic acid phosphatase enzyme protein in serum are not specific for prostatic carcinoma.

Acid Phosphatase↗
PubMed1981

The effect of manipulation of the prostate gland on serum prostate-specific acid phosphatase measured by radioimmunoassay.

We investigated the effects of digital prostatic palpation, cystoscopy, and biopsy of the prostate on the concentrations of serum prostate-specific acid phosphatase (PAP) measured by radioimmunoassay. Serum concentrations of PAP in patients with normal or hyperplastic prostates did not exceed the upper limit of our reference range (4 microgram per liter) during the 48 hr after digital prostatic palpation. The serum concentrations of PAP did not significantly increase in patients with carcinomatous prostates after digital examination of the prostate. Serum PAP did increase in patients with benign prostatic hyperplasia soon after cystoscopy of biopsy of the prostate. No diurnal variation in the serum concentrations of PAP during the follow-up of 48 hr was detected in the patient groups with normal, benign hyperplastic, or carcinomatous prostates not subjected to rectal examination.

Acid Phosphatase↗
PubMed1981

Effectiveness of radioimmunoassay of human prostate-specific acid phosphatase in the diagnosis and follow-up of therapy in prostatic carcinoma.

The radioimmunoassay of human prostate-specific acid phosphatase and the measurement of the catalytic activity of acid phosphatase using p-nitrophenyl phosphate as substrate were compared in the diagnosis and follow-up of therapy of prostatic cancer patients. We monitored 17 patients without metastases and eight patients with metastases for 12 months. We detected elevation of the catalytic activity of acid phosphatase [the upper limit for the reference range was mean + 2 (S.D.)] in 24% of the sera of all these patients (n = 25), and the concentration of prostate-specific acid phosphatase measured by radioimmunoassay [the upper limit for the reference range was mean + 3 (S.D.)] was elevated in 80% of these samples before therapy. The radioimmunological measurement of prostate-specific acid phosphatase was therefore more efficient in detecting prostatic cancer than was measurement of the catalytic activity. Favorable effects of the various forms of endocrine treatment were detected more clearly by the measurement of immunoassayable prostatic acid phosphatase than by the measurement of catalytic activity. Activation of the disease during various forms of endocrine treatment of prostatic carcinoma is possibly more efficiently signaled by radioimmunoassay than by measurement of catalytic activity.

Acid Phosphatase↗
PubMed1980

Rapid radioimmunoassay for prostate-specific acid phosphatase in human serum.

We describe a rapid radioimmunoassay for human prostatic acid phosphatase (EC 3.1.3.2) in serum, with use of monospecific antisera raised in rabbits against the primary highly purified acid phosphatase (pl 4.9) from human prostates, and with a second antibody-polyethylene glycol porecipitation. This radioimmunoassay is sensitive and can be performed within 5 h. Concentrations of the immunoreactive acid phosphatase in sera of healthy men (n = 394) ranged from 0.3 to 3.6 microgram/L (mean 1.94, SD 0.66 microgram/L). Concentrations of the enzyme in sera of men with benign prostatic hyperplasia (n = 56) or with carcinoma of nonprostatic origin (n = 24) were identical with those of the reference group. Serum concentrations of immunoreactive prostatic acid phosphatase of patients with occult, non-metastatic, and metastatic prostatic carcinoma varied from 1.7 to 9.3 (n = 9), 4.2 to 59.4 (n = 12), and 20 to 198 (n = 10) microgram/L, respectively. The amount of immunoassayable prostatic acid phosphatase was unchanged for at least five days in serum stored at 4 degrees C.

Acid Phosphatase↗
PubMed1979

Human prostatic acid phosphatases: purification of a minor enzyme and comparisons of the enzymes.

The minor enzyme of human prostatic acid phosphatases (pI 5.5) with high specific activity (orthophosphoric monoester phosphohydrolase, acid optimum, EC 3.1.3.2) has been purified for the first time as a pure enzyme protein. The enzyme was a single protein when examined by polyacrylamide gel electrophoresis and isotachophoresis. The specific activity was 1080 micromole per (min X mg) for hydrolysis of 5.5 mmole per liter of p-nitrophenylphosphate at pH 4.8 and 37 C. The purification coefficient was 540 and the recovery of enzyme activity was 2 per cent. The molecular weight of the enzyme subunit when measured by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate was 54,000. The Km of the purified enzyme was 3 X 10(-4) mole per liter for p-nitrophenylphosphate. An antiserum to this enzyme was prepared. The enzyme was cross-reactive with the main enzyme (pI 4.9) of human prostatic acid phosphatases in immunoelectrophoresis. No precipitin arc with the acid phosphatase in the serum of a prostatic carcinoma patient could be shown. Antiserum to the main enzyme caused a precipitin line with the same serum sample.

Acid Phosphatase↗
PubMed1978

Serum steroids in normal males and patients with prostatic diseases.

The subjects investigated comprised 57 normal males between 30 and 80 years of age; 40 patients between 50 and 80 years of age suffering from benign prostatic hypertrophy (BPH), and 11 untreated prostatic carcinoma (Ca) patients aged between 57 and 79 years. Serum concentrations of oestradiol, pregnenolone, progesterone, 17alpha-hydroxyprogesterone, androstenedione, testosterone, 5alpha-dihydrotestosterone and androsterone were determined from a single serum sample (1.6 ml). Oestradiol was determined by an automated non-chromatographic radioimmunoassay, while other steroids were determined by radioimmunoassays, after solvent extraction and chromatographic purification on Lipidex-5000TM microcolumns. When patient groups were compared with the 25 normal males between 50 and 80 years of age, several conclusions could be drawn. Serum concentrations of 5alpha-dihydrotestosterone (P less than 0.01) and 17alpha-hydroxyprogesterone (P less than 0.001) were both significantly higher in the BPH patients when compared with the normal males. This trend was also apparent in the serum concentrations of progesterone and testosterone in the older BPH patients. Although the mean concentrations of 5alpha-dihydrotestosterone and 17alpha-hydroxyprogesterone were slightly higher in carcinoma patients than normal males, these differences were not statistically significant. No differences were seen in the concentrations of pregnenolone, androstenedione, androsterone and oestradiol between normal subjects and patients with BPH or prostatic Ca.

Adult↗
PubMed1978

Characterization of the principal human prostatic acid phosphatase isoenzyme, purified by affinity chromatography and isoelectric focusing. Part II.

The principal enzyme of human prostatic acid phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2], which had been highly purified by affinity chromatography, isoelectric focusing, and gel filtrations, was shown to be homogeneous at pH 5.0 by sedimentation equilibrium analysis. The amino acid composition was determined and the sedimentation coefficient of the native molecule measured. The relative molecular mass was 89,000 at pH 5.0, as measured by analytical ultracentrifugation. The Km-value of the enzyme for p-nitrophenyl phosphate as substrate is 1.8-10(-4) mol/liter. I also examined substrate speificity, different inhibitors, and the effects of pH, temperature, and serum on the enzyme activity.

Acid Phosphatase↗
PubMed1978

Purification of human prostatic acid phosphatase by affinity chromatography and isoelectric focusing. Part I.

The main isoenzyme of human prostatic acid phosphatases was purified by affinity chromatography on L(+)-tartrate linked to agarose and by isoelectric focusing. The enzyme was a single protein when examined by polyacrylamide gel electrophoreses, either as a native protein or in the presence of sodium dodecyl sulfate. The analytical recovery of enzyme activity was 19%. The specific activity was 40 18 mumol/(min X mg) for hydrolysis of 5.5 mmol/liter p-nitrophenyl phosphate at pH 4.8 and 37 degrees C. The purification factor was as great as 1900. The molecular weight of the enzyme as measured by gel filtration was 109 000 and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate 54 000, indicating that the enzyme had been isolated in the dimer form. By this method we have achieved the best purification of human prostatic acid phosphatase so far.

Acid Phosphatase↗
PubMed1978

Serum prostate-specific acid phosphatase: development and validation of a specific radioimmunoassay.

We describe radioimmunoassay for human prostatic acid phosphatase [orthophosphoric-monoester phospho-hydrolase (acid optimum), EC 3.1.3.2] in serum, with use of monospecific antisera raised in rabbits against highly purified acid phosphatase from human prostates. The antiserum did not cross react with partly purified acid phosphatases from human spleen, erythrocytes, or synovial tissues. 125I-labeled acid phosphatase was prepared by a Chloramine T method, and the bound and free antigen was separated in the assay by use of anti-rabbit gamma-globulin raised in sheep. Uniform low nonspecific binding of the [125I]acid phosphatase was achieved by using acid-phosphatase-free serum to prepare standard curves and diluted samples of serum with high acid phosphatase activities. Concentrations of immunoreactive acid phosphatase in the serum of healthy men ranged from less than 1 to 10 microgram/liter and for 12 patients with advanced prostatic carcinoma between 100 and 500 microgram/liter. The concentrations of the enzyme in sera of patients with benign prostatic hyperplasia were very similar to those in sera of the reference group.

Acid Phosphatase↗
PubMedDate not supplied

Activin-A, but not inhibin, regulates 17beta-hydroxysteroid dehydrogenase type 1 activity and expression in cultured rat granulosa cells.

17beta-Hydroxysteroid dehydrogenase type 1 (17HSD type 1) catalyzes the reduction of estrone (E(1)) to biologically more active estradiol (E(2)). In the present study, the effect of activin, inhibin, and follistatin on 17HSD activity and 17HSD type 1 expression in cultured, unluteinized rat granulosa cells was examined. Furthermore, the effects of these hormones on 17HSD type 1 expression were compared with the expression of P450 aromatase (P450arom). Rat granulosa cells were pre-incubated in serum-free media for 3 days, followed by a 2-day treatment with activin, inhibin, follistatin and 8-Br-cAMP. Activin in increasing concentrations appeared to effect a dose-dependent increase in 17HSD activity. In addition, increasing concentrations of activin also increased 17HSD type 1 mRNA expression. Addition of 8-Br-cAMP at concentrations of 0.25 and 1.5 mmol/l together with activin significantly augmented the stimulatory effects of activin alone in the cultured cells. Neither inhibin, nor follistatin, either alone or in combination with 8-Br-cAMP, had any notable effects on 17HSD activity and 17HSD type 1 expression. Preincubation of activin with increasing concentrations of follistatin significantly diminished the stimulatory effect of activin. In the presence of follistatin, activin did not significantly increase the 8-Br-cAMP-induced 17HSD activity and 17HSD type 1 expression. The culturing of granulosa cells in the presence or the absence of inhibin or follistatin with or without 8-Br-cAMP did not alter the effect of these peptides on P450arom expression in rat granulosa cells as judged by Northern blot analysis of total RNA. However, cAMP-induced P450arom expression was enhanced by activin treatment, except when follistatin was present. This is in line with the suggested role of follistatin as an activin-binding protein, which limits the bioavailability of activin to its membrane receptors. Thus, the results support the notion of a paracrine/autocrine role of activin in follicular steroidogenesis of growing follicles.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7.

Two 17beta-hydroxysteroid dehydrogenases (17HSDs), type 1 and type 7, are enzymes of estradiol biosynthesis, in addition to which rodent type 1 enzymes are also able to catalyze androgens. Both of the 17HSDs are abundantly expressed in ovaries, the type 1 enzyme in granulosa cells and type 7 in luteinized cells. The expression of 17HSD7, which has also been described as a prolactin receptor-associated protein (PRAP), is particularly up-regulated in corpus luteum during the second half of rodent pregnancy. A moderate or slight signal for mouse 17HSD7/PRAP mRNA has also been demonstrated in samples of placenta and mammary gland, for example. Human, but not rodent, 17HSD1 is expressed in placenta, breast epithelium and endometrium in addition to ovaries. A cell-specific enhancer, silencer and promoter in the hHSD17B1 gene participate in the regulation of type 1 enzyme expression. The enhancer consists of several subunits, including a retinoic acid response element, the silencer has a binding motif for GATA factors, and the proximal promoter contains adjacent and competing AP-2 and Sp binding sites.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Morphological and genetic abnormalities in prediction of recurrence in radically operated colorectal cancer.

BACKGROUND: We analyzed clinicopathological variables, cell proliferation activity and genetic aberrations related to colorectal cancer in order to recognize clinically usable predictive markers of cancer recurrence. MATERIALS AND METHODS: A total of 111 patients radically operated upon because of primary colorectal cancer in 1986-1991 were studied. Loss of heterozygosity (LOH) at 18q21 and replication errors were studied by polymerase chain reaction and fragment analysis. Expression of p53 protein and that of Ki-67 were studied using immunohistochemical methods. RESULTS: LOH at 18q21 was the only factor associated with recurrence (P = 0.03), and indicated a worse five-year cumulative survival rate (42%) than did LOH-negativity (72%) in cases of Dukes classes B and C. Expression of p53 protein indicated recurrence (P = 0.07), short disease-free time and poor survival (P = 0.03) in Dukes class A cases. CONCLUSIONS: LOH at 18q21 appears useful in predicting recurrence and poor survival in cases of Dukes classes B and C, as does p53 expression in class A cases.

Adult↗
PubMedDate not supplied

Effect of conjugation on the biodistribution of 111In-labelled anti-PAP and anti-PSA monoclonal antibodies examined in nude mice with PC-82 human tumor xenografts.

The effect of conjugation on the biodistribution of 111In-labelled antibodies was studied in nude mice carrying human prostatic cancer xenografts (PC-82). Two monoclonal antibodies and their fragments raised against human prostate-specific acid phosphatase (PAP) and prostate-specific antigen (PSA) were used. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent, or, alternatively, 1-(p-aminobenzyl)diethylenetriaminepentaacetic acid (NH2-Bz-DTPA) was attached as a linker to the carbohydrate components of the parent molecules. The conjugation method, the amount of circulating antigen and the size of the antibody component affected the blood clearance of the labelled derivatives. F(ab')2 fragments displayed a faster blood clearance than the corresponding derivatives of intact IgG1s. Aminobenzyl derivatives of anti-PAP-IgG1 showed a faster blood clearance than the corresponding CA-DTPA derivatives, but, in the case of derivatives of anti-PSA-IgG1, this was less clear, possibly due to the high PSA concentrations in the mouse sera. All the derivatives studied accumulated in the liver independently of the size of the antibody derivative, most probably due to the formation of antigen-antibody complexes. All CA-DTPA derivatives showed a higher kidney accumulation than the corresponding aminobenzyl derivatives. CA-DTPA-anti-PAP-F(ab')2 fragments showed a higher kidney uptake than the corresponding anti-PSA-F(ab')2 derivatives, since a large fraction of the latter are complexed with circulating antigen, thereby slowing down its reabsorption by the kidney. In addition, the lower kidney accumulation for anti-PSA-F(ab')2 fragments might be, at least partly, due to the electronegative charge of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMedDate not supplied

Effect of unlabelled monoclonal antibodies on the biodistribution of 111In-labelled anti-prostate-specific acid phosphatase monoclonal antibodies in the mouse model.

In order to optimize methods developed for the radioimaging of prostatic cancer, the effect of unlabelled monoclonal antibodies (MoAbs) on the biodistribution of 111In-labelled MoAbs was studied in nude mice carrying human prostatic cancer xenografts (PC-82). Since the intact IgG and its F(ab')2 fragment have different clearance patterns from the blood, we also studied which of these antibody forms is preferable for use as the unlabelled antibody, when injected prior to, simultaneously with, or following the injection of the labelled antibody. Due to their faster blood clearance, F(ab')2 fragments displayed higher tumour-to-blood ratios than the corresponding anti-prostate-specific acid phosphatase (anti-PAP) IgG1. However, tumour-to-blood ratios increased when the amount of the labelled anti-PAP-IgG1 was increased (from 10 micrograms to 25 micrograms) and the biodistribution measurements were carried out after a prolonged period (216 h). When a combination of labelled IgG1 (1, 10 micrograms) and unlabelled IgG1 (200 micrograms-300 micrograms) was used, tumour-to-blood ratios could not be improved. Contrary to what was observed with the intact IgG1, labelled F(ab')2 fragments did not display a dose-dependent accumulation in the tumour. A combination of labelled F(ab')2 fragments and unlabelled IgG1 resulted in a slight increase in tumour-to-blood ratios, but the administration of labelled F(ab')2 fragments with unlabelled F(ab')2 fragments resulted in a significant decrease (p = 0.04) in tumour-to-blood ratios. Liver-to-blood ratios could be decreased by using either a combination of unlabelled and labelled IgG1 (at ratios of 30:1, or 200:1), or a combination of unlabelled IgG1 and labelled F(ab')2 fragments (at ratios of 50:1, or 100:1), or a combination of the unlabelled and labelled F(ab')2 fragments (at a ratio of 50:1). The decrease of liver-to-blood ratios was independent of the mode of administration of the unlabelled substances. A "rinse" with an additional dose of unlabelled IgG1, 24 h before the sacrifice, resulted in even lower liver-to-blood ratios. The results obtained from this study suggest that, of the combinations investigated, to increase tumour-to-blood ratios and decrease liver-to-blood ratios thereby improving the radioimaging of prostatic cancer, the best one consists of 111In-labelled anti-PAP-F(ab')2 fragments and unlabelled anti-PAP-IgG1.

Acid Phosphatase↗