PubMed Health⌕ Search

Biomedical subjects

J Müntzing

Publications and source records attributed to J Müntzing.

At least 19 recordsLinked to original sources
PubMed1989

An immunohistochemical technique for localization and semiquantitation of estramustine-binding protein (EMBP) in rat and human prostate.

An immunohistochemical technique for determination of "estramustine-binding protein" (EMBP) in rat prostate is described. The localization and staining intensity of this protein were correlated to prostatic morphological structures in intact animals and at different time intervals after androgen deprivation by castration. EMBP was found almost exclusively in epithelial cells, while the fibromuscular stroma seemed to be negative. Intracellularly, immunostaining was confined to the cytoplasm, but was absent in nuclei. In intact rats, acinar lumina demonstrated heavy immunostaining, indicating secretion of EMBP. Orchiectomy caused a diminution of EMBP expression as well as secretion, suggesting that EMBP synthesis is under androgenic regulation. Human benign hyperplastic and cancerous prostatic specimens were also examined. All human specimens examined so far exhibited positive epithelial staining although of varying intensity. Therefore, this immunohistochemical technique may be used for studying the correlation of EMBP with tumor malignancy grade and for clinical investigations of how various treatments affect EMBP expression in prostatic carcinomas.

Animals↗
PubMed1989

Effect of treatment on the expression of estramustine-binding protein (EMBP) in prostatic cancer patients: an immunohistochemical study.

Estramustine-binding protein (EMBP) was determined immunohistochemically in prostatic cancer (PC) specimens taken from patients before and after therapy. The EMBP staining intensity was correlated with the tumor malignancy grade in untreated PCs. The effect of various treatments (i.e., androgen-withdrawal therapy, treatment with estramustine phosphate or radiation) on the expression of EMBP was also investigated. Although a rabbit polyclonal antiserum raised against rat EMBP was used all through the study, all untreated PCs (n = 53) examined so far displayed a positive immunoreaction. The staining intensity was higher in moderately and poorly differentiated than in well-differentiated tumors. Furthermore, two types of staining patterns were observed, that is, a diffuse type in about 70% and a focal in the remaining cases, which might reflect the multifocal appearance of PCs. The prognostic significance of these staining patterns is discussed. Irrespective of the treatment used, EMBP staining was reduced to lower or undetectable levels in PCs where cytological as well as clinical regression were indicated after 6-30 months of therapy. In nonresponders or patients with refractory disease, however, EMBP expression reappeared and returned to pretreatment levels. In a short-term follow-up, the diminuation of EMBP was evident as early as 10 days after androgen-withdrawal therapy and persisted as long as the patient responded to therapy. When estramustine phosphate was given as secondary treatment to hormone refractory PCs, EMBP decreased to undetectable levels in 3/4 of the specimens, suggesting response to therapy. In conclusion, a decreased EMBP staining was well correlated with favorable cytological regression as well as with clinical regression, whereas unchanged staining intensity was indicative of clinical progression and a poor cytological regression grade. The high levels of EMBP in moderately and poorly differentiated tumors as well as in relapsing PCs, despite continued androgen withdrawal, strongly support a regulation of EMBP that is not under androgenic control. Based on the present findings, we suggest the use of EMBP as a therapy marker. Provided that immunohistochemical measurements can be performed on fine-needle aspirates, EMBP analysis may be a direct and early means to distinguish between responding patients and nonresponders.

Carrier Proteins↗
PubMed1988

Regulation of prostatic growth. Growth-limiting mechanisms in the rat ventral prostate.

The possibility that a prostatic chalone is a factor regulating growth of the gland was investigated in rats submitted to hemiprostatectomy to reduce the level of a hypothetical circulating chalone. No evidence of regeneration was found 4 weeks postoperatively. Orchiectomized rats with intrasplenic, intramuscular or intraprostatic implants of ventral prostatic tissue from other orchiectomized rats, were given androgen. The cell divisions in the prostatic tissue did not end until the total cell number was 150-170% of that in control rats. These results indicate that other factors than a prostatic chalone have a dominant role in the mechanism limiting prostatic growth. As introduction of an artificial stroma led to increased prostatic growth, it appears likely that the fibromuscular stroma is one of the factors controlling growth of the prostatic epithelial cells.

Androgens↗
PubMed1987

Ultrastructure and immunohistochemistry of the lateral prostate in aged rats.

Ultrastructural, histological, and immunohistochemical studies were performed on lateral prostates of 1) aged rats from different strains, 2) rats permitted different levels of sexual activity, and 3) castrated rats. Antibodies against the following proteins were used as immunohistochemical markers: SVS II from seminal vesicle, LP 28 from lateral prostate, acid phosphatase isoenzymes from ventral prostate, transglutaminase from coagulating gland, and a commercial monoclonal antibody against cytokeratin. SVS II is a marker of lateral prostatic secretion, while immunoreactions to LP 28 and acid phosphatase (pI 7.1) were cytoplasmic. In aged animals the amount of intracellular secretion is decreased, and focally metaplastic transformation can be visualized by using immunohistochemical markers. Epithelial ultrastructure varied considerably with experimental conditions. Intensive sexual activity resulted in increased polymorphism and increased number of secretory granules within the glandular cells, while castration was followed by a rapid loss of secretory material. Also, in rats older than 10 months, a reduction in the number of secretion granules was common. The epithelium developed a positive immunoreaction to transglutaminase antibodies that were not observed in juvenile glands. Cells, presumably macrophages, which had an intense immunoreactivity for transglutaminase, were increased in number both within and outside the prostatic acini of aged rats. The possible interaction between secretory SVS II, a substrate of transglutaminase, the release of this enzyme from macrophages or its reflux from coagulating glands, the spontaneous cellular exfoliation that is due to decreased androgen levels, and dietary noxae may be of importance in the development of lateral prostatic nonbacterial inflammation in aged rats.

Acid Phosphatase↗
PubMed1979

Pilot study on the growth inhibition by estramustine phosphate (Estracyt) of rat mammary tumours sensitive and insensitive of oestrogen.

Rat mammary tumours induced by 7,12-dimethylbenz(a)anthracene had a higher concentration of 3H and 14C than muscle after injection of estramustine phosphate labelled with 3H in the oestrogen moiety and 14C in the alkylating moiety. Thin-layer chromatography showed that dephosphorylated estramustine phosphate was present in the tumours but no free oestradiol-17beta. The uptake of the drug in the tumours was parallelled by a dose dependant retardation of tumour growth and a prevention of tumour number increase. Estramustine phosphate also retarded growth of mammary tumours resistant to treatment with oestradiol-17 beta. It is concluded that estramustine phosphate has a greater effect on tumour growth than oestrogen.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Prostatitis in the rat.

A high incidence of spontaneous, non-acute, age-dependent prostatitis was observed in the lateral prostate of Copenhagen rats and Wistar rats. The lumen of infected acini was filled with polymorphonuclear leucocytes, shed epithelial cells and cell residues. Epithelial cells lining such acini showed degenerative changes. Lymphocytes and macrophages were seen in the stroma. A histochemically observed increase in acid phosphatase and beta-glucuronidase activity in affected epithelial cells may indicate an increased lysosomal activity. Some bacteriological cultures of infected lateral prostates were positive for Proteus vulgaris and diphtheroids. It is suggested that this spontaneous rat prostatitis may be a useful model for the study of the pathogenesis and treatment of human non-acute prostatitis.

Acid Phosphatase↗
PubMed1979

Chalones and stroma as possible growth-limiting factors in the rat ventral prostate.

In an attempt to determine the mechanism that limits the growth of the rat ventral prostate, atrophied ventral prostates from orchiectomized inbred rats were implanted into the ventral prostate of other inbred rats. Under the influence of endogenous or exogenous androgen the DNA content of the ventral prostates was increased above normal. This indicates that there is no soluble growth inhibitor diffused in the normal prostate in a concentration sufficient to block cell divisions of the epithelial cells. In other experiments pieces of plastic sponge were implanted into the rat ventral prostate. Orchiectomy and subsequent androgen treatment led to an increased cell number in the prostate. Histologic examination revealed an ingrowth of loose connective tissue and also of normal-looking prostatic tissue in the sponge. The results suggest that implantation of pieces of sponge induced increased growth of the fibromuscular stroma and a secondary proliferation of the epithelial cells. A growth control of the prostatic epithelial cells by the fibromuscular stroma is suggested.

Androgens↗
PubMed1979

A rat prostatic adenocarcinoma as a model for the human disease.

A transplantable, metastasizing prostatic adenocarcinoma (Tumor I) in Lobund Wistar rats was examined for activity and distribution of five hydrolytic enzymes and for ability to accumulate radioactive zinc. The results suggest that the tumor had arisen in the ventral lobe of the prostate and that its growth was not affected by orchiectomy, adrenalectomy, or replacement treatment with exogenous androgen or corticosteroids. The androgen independency of the tumor was further shown by the low uptake of 3H-testosterone, in contrast to the high uptake in the ventral prostate. Tumor growth was retarded by Cytoxan but not by 5-fluorouracil, Estracyt, or streptozotocin, three agents clinically effective in the treatment of some patients with prostatic cancer resistant to endocrine therapy. It is concluded that this tumor in Lobund Wistar rats may be an adequate model for human prostatic cancers resistant to the agents mentioned above.

Acid Phosphatase↗
PubMed1979

Direct and indirect effects of docosanol (IK.2), the active principle in Tadenan, on the rat prostate.

To better understand the mode of action of Tadenan, a drug used in the treatment of benign prostatic hyperplasia, the effect of its active principle docosanol, IK.2, was investigated in rats. IK.2 had no effects on the weight and histologic appearance of the prostate in intact rats but increased the RNA/DNA quotient in the ventral prostate. The plasma concentrations of luteinizing hormone and testosterone were reduced. In orchiectomized animals IK.2 increased the weight of the prostate and the adrenals. In adrenalectomized, orchiectomized animals IK.2 did not increase prostatic weight but on the contrary caused a further weight reduction. IK.2 had a thymolytic effect in intact rats but not in adrenalectomized rats in which the thymus weight was increased. The results indicate that IK.2 increases adrenal steroid secretion. The supposedly higher concentration of adrenal androgens causes a stimulation of the prostate most easily discernible in orchiectomized animals. The further weight reduction of the ventral prostate in orchiectomized, adrenalectomized animals, and the increased thymus weight in adrenalectomized animals after IK.2 administration may suggest that IK.2 has effects other than the stimulatory effect on the adrenals.

Adrenalectomy↗
PubMed1978

Enzyme activity and distribution in rat prostatic adenocarcinoma.

The activity and distribution of acid phosphatase, alkaline phosphatase, nonspecific esterases, beta-glucuronidase, and aminopeptidase were examined in the transplantable R-3327 rat prostatic adenocarcinoma and compared with those in the four prostatic lobes of the rat. Both the well and poorly differentiated tumor cells in R-3327 carcinoma were characterized by high activities of beta-glucuronidase and aminopeptidase. The poorly differentiated cells had a high alkaline phosphatase activity. The enzymatic profile of the R-3327 adenocarcinoma closely resembled that of the anterior and dorsal prostate. The origin of the tumor in one of these prostatic lobes is probable, but not certain.

Adenocarcinoma↗
PubMed1978

Mammary tumour inhibition and subacute toxicity in rats of prednimustine and of its molecular components chlorambucil and prednisolone.

Prednimustine, a chlorambucil ester of pregnisolone, retarded growth of DMBA-induced mammary tumours in rats and reduced the number of tumours. A combination of chlorambucil and prednisolone (C + P) in the same proportion as in prednimustine, had similar effects, 8 and 26 mg per kg of the C + P combination being equipotnet to 16 and 64 mg per kg of prednimustine, respectively. The mortality figures suggested that prednimustine was considerably less toxic than equipotent doses of C + P. This toxicity difference was confirmed in a parallel investigation of the subacute toxicity in rats of prednimustine and C + P. This study showed that the mortality, reduction of lymphocytes and platelets, and bone marrow depression was much lower after pregnimustine than after equimolar amounts of the C + P combination. The results suggest that the low toxicity of prednimustine makes this drug a better cytostatic agent than the C + P combination treatment.

Animals↗
PubMed1977

Inhibitory effects of Estracyt on R-3327 rat prostatic carcinoma.

Estracyt (estramustine phosphate) injected intraperitoneally, 100 mg, per Kg. three days a week for four weeks, retarded growth of the R-3327 tumor in intact rats and in orchiectomized rats given androgen. The growth inhibition was accomplished by reduction of tumor deoxyribonucleic acid concentration and of the activities of acid phosphatase, leucine aminopeptidase, and other hydrolases. Histologic examination revealed cellular necrosis particularly prominent in the orchiectomized, androgen-treated rats. Estracyt did not affect the uptake of 65-Zn in the tumors but markedly reduced the high uptake in the dorsolateral prostate. There was no accumulation of 3H or 14C in the tumors after intravenous administration of 3H, 14C-labeled Estracyt, but the isotope concentrations decreased much in the same way as they decreased in the dorsolateral prostate. The isotopes were retained in the ventral prostate, where their concentrations were approximately twenty times higher than those in the muscle four hours after injection. The results demonstrate the value of the R-3327 tumor in the evaluation of drugs of potential clinical use for the treatment of prostatic cancer. The results also show that Estracyt has an antitumor effect which is not dependent on the antigonadotropic action of the drug.

Acid Phosphatase↗
PubMed1977

Hormonal control of zinc uptake and binding in the rat dorsolateral prostate.

The zinc uptake in the dorsolateral prostate of rats was studied after different hormonal manipulations. Orchiectomy reduced the uptake of 65Zn. Administration of estradiol benzoate to orchiectomized rats doubled the 65Zn uptake, a phenomenon which was not observed in orchiectomized-adrenalectomized rats. Adrenalectomy in orchiectomized rats had no effect on the concentration of radioactivity beyond the castration-induced decrease. A prolactin release inhibitor, 6-methyl-8-erogelenylacetamide, reduced the radioactivity concentration without changing the weight of the gland. Cyproterone acetate reduced the weight but not the radioactivity concentration. The concentration of 65Zn in the ventral prostate was not changed by orchiectomy, adrenalectomy, or the administration of estradiol benzoate, prolactin release inhibiors, or cyproterone acetate. The results suggest an important role for prolactin in the zinc uptake in the dorsolateral prostate but not in the ventral prostate.

Acetamides↗
PubMed1976

The growth characteristics of metastases from experimental renal tumors.

Wistar-Furth rats and BALB/c mice were implanted with tumor cells from metastases or primaries of an experimental Wilms' tumor or an experimental renal cell adenocarcinoma. The survival time, metastasis formation and growth of the primary tumor after implantation of metastatic tumor cells did not exceed those found after implantation of tumor cells from the tumor primaries. It is concluded that the higher growth rate usually found in metastases is not necessarily due to a selection of metastatic cells with a short cell growth cycle but that there are other environmental factors enhancing the growth of metastases.

Adenocarcinoma↗
PubMed1976

Histochemical and ultrastructural study of prostatic tissue from baboons treated with antiprostatic drugs.

Histochemical and ultrastructural investigation of the prostate in baboons treated parenterally with saline revealed that the epithelial cells in the caudal prostatic lobe possess very high acid phosphatase activity, moderate nonspecific esterase activity and alkaline phosphatase activity, and little or no amino-peptidase or beta-glucuronidase activity. Only a few lipofuscin granules were found. Ultrastructurally, the epithelial cells had a characteristic polar appearance with a supranuclear zone dominated by large secretory vacuoles. Secretory granules were abundant in the apical zone. No clear difference was found between the cranial and the caudal prostate except that the acid phosphatase activity of the epithelial cells was much lower in the former. In baboons treated with estraumustine phosphate, diethylstilbestrol diphosphate, or with flutamide, i.e., drugs used in the treatment of advanced prostatic carcinoma, the epithelial cells in the caudal prostatic lobe showed a varying degree of atrophy, which was least in the flutamide-treated animals. The histologic changes were accompanied by only minor changes in the enzyme activities, but the number of histochemically demonstrable lipofuscin granules were substantially increased, a finding confirmed by electron microscopy. The drugs did not notably affect the cranial prostate. The findings showed that the caudal, but not the cranial, lobe of the prostate of the baboon resembles the human prostate and can be affected by drugs known to have a desirable effect on the carcinomatous human prostate.

Acid Phosphatase↗
PubMed1976

The absorption metabolism, and excretion of Estracyt (NSC 89199) in patients with prostatic cancer.

Estraumustine phosphate (estradiol, 3-N-[bis(2-chloroethyl)-] carbamate-17beta-dihydrogenphosphate (Estracyt) labeled with 3H in the estradiol moiety and 14C in the carbamate moiety was synthesized, and its absorption, metabolism, and excretion were studied after oral administration to three patients with prostatic carcinoma. One of the patients was also given the same dose by intravenous injection. In addition to monitoring isotope levels in peripheral blood, urine, and feces, samples of portal vein blood were obtained through a catheter in the umbilical vein. Analyses of portal blood samples revealed that most of the estramustine phosphate was dephosphorylated to estramustine during absorption. Estramustine was found to be the major metabolite in peripheral blood after oral as well as after intravenous administration. The urinary excretion data appeared to warrent the conclusion that most of the carbamate ester of estraumustine is hydrolyzed before it is excreted. In the patient given estramustine phosphate by both routes the absorption of the compound when given by mouth was found to be approximately 75 per cent.

Administration, Oral↗