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H Weisser

Publications and source records attributed to H Weisser.

28 records · Page 2Linked to original sources
PubMed1994

5 alpha-reductase inhibition by finasteride (Proscar) in epithelium and stroma of human benign prostatic hyperplasia.

Finasteride is a specific 5 alpha-reductase inhibitor that has been shown to reduce the size of human benign prostatic hyperplasia (BPH) by inhibiting the intraprostatic conversion of testosterone to 5 alpha-dihydrotestosterone. The aim of the present in vitro study was to describe in more detail the inhibitory effect of finasteride on 5 alpha-reductase in epithelium and stroma of human BPH. 5 alpha-Reductase activity in epithelium and stroma was inhibited dose-dependently by finasteride. The mean IC50 (50% inhibitory concentration) values, determined in the presence of various testosterone concentrations, were generally 2- to 4-fold lower in epithelium than in stroma. With finasteride concentrations greater than 5 nM, competitive inhibition of 5 alpha-reductase occurred both in epithelium and stroma. The mean inhibition constant Ki[nM +/- SEM] was 7 +/- 3 and 31 +/- 3 in epithelium and stroma, respectively. In the presence of finasteride concentrations < or = 5 nM, the epithelial 5 alpha-reductase seems to be inhibited in an uncompetitive manner, whereas such low finasteride concentrations cause either no inhibition (1-2 nM) or competitive inhibition (5 nM) in stroma. Our present study provides evidence that the inhibitory effect of finasteride on 5 alpha-reductase is much stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.

5-alpha Reductase Inhibitors↗
PubMed1994

Effect of medium exchange rate on colony growth of the human tumor cell line MDA-231 cloned within the perfused capillary cloning system.

The conventional human tumor stem cell assay is limited by the lack of flexibility for drug scheduling with single agents and its inability to test drug combinations. Recently, we described the cloning of tumor cell lines within porous glass capillary tubes which allow free exchange of substances. The present study describes the influence of various perfusion modalities on the colony growth of the human tumor cell line MDA-231 cloned within the perfused capillary cloning system (PCCS). Colony growth of tumor cells within the PCCS is strongly dependent on perfusion tube volume, flow rate and duration of perfusion with growth medium. Best colony growth was achieved using a perfusion tube volume of 12 ml resulting in a cloning efficiency of 36.3%. Continuous perfusion with fresh medium did not improve the cloning efficiency; in fact, colony growth was hampered compared to colony growth within unperfused porous capillaries. However, cloning efficiency was acceptable when continuous perfusion was started at day 6 (26.4%) instead of day 0 (17.2%), or when a short perfusion with high volume (12 ml/h) was discontinued after 1 h at day 0. In contrast to the conventional capillary cloning system the PCCS has the potential for investigating secretion and kinetics of tumor-specific factors and the effect of growth-stimulating or growth-inhibiting drugs.

Breast Neoplasms↗
PubMed1993

[Androgen and estrogen metabolism in human benign prostatic hyperplasia (BPH)].

Among all androgen metabolizing enzymes within the human prostate 5 alpha-reductase is the most powerful one. In the epithelium its activity decreases with age, while in the stroma it remains constant over the whole age range. Thus, in older prostates with benign hyperplasia the activity of 5 alpha-reductase is almost the same in both compartments. The same holds true for the DHT content, being highest in the epithelium of prostates from young men. With age it decreases to levels similar to those in the stroma. In contrast to DHT, estrogens are increasingly accumulated in the stroma with advancing age, while in the epithelium the estrogen level remains constant over the whole age range. The age-dependent decrease of the DHT level in the epithelium and the increase of the estrogen level in the stroma lead to a significant increase of the estrogen/androgen ratio. This could be of pathobiological importance for BPH development.

Aging↗
PubMed1993

Distribution of immune effector cells within an experimental osteosarcoma of the nude rat.

In vivo studies on osteosarcoma are limited by the relative low incidence of this tumor in man. Therefore, there is a high dependence on a reliable experimental tumor model. In previous studies, a transplantable osteosarcoma of the athymic nude rat was established. In the present study the content and pattern of distribution of immune effector cells within this osteosarcoma were investigated by immunohistochemistry, and were related to histomorphologic findings. The absence of T-like cells within the tumor of 1- to 2-month-old athymic nude rats was shown using the T-lymphocyte-specific monoclonal antibody OX-19. In contrast, OX-6-positive cells, representing B lymphocytes and macrophages, were distributed throughout the whole tumor with a discrete accumulation at the borderline between the peripheral proliferative tumor tissue and the central necrotic area. Using the macrophage-specific monoclonal antibody ED1 we found the accumulation of mononuclear cells to consist mainly of macrophages. The distribution of these macrophages was closely related to histomorphologic tumor characteristics: the major proportion was found in the proliferative peripheral part of the tumor with highest macrophage content at the border to the central necrosis. As the measurement of tumor necrosis in osteosarcoma plays an important role in the judgement of therapeutic response, this distinct delimitation of tumor necrosis by macrophages could be helpful in the evaluation of therapeutic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cloning of human tumor cell lines in porous glass capillary tubes: a further development of the human tumor stem cell assay.

The conventional human tumor stem cell assay for cloning tumor cells for drug sensitivity testing is limited by its inability to test drug combinations. In an attempt to overcome this limitation, we cloned tumor cell lines within porous glass capillary tubes. In contrast to plastic porous tubes, the porous glass membranes were transparent, and colony formation could be judged on an inverted microscope. Human as well as animal cell lines showed sufficient colony growth. Colonies formed within these porous tubes were homogeneously distributed, and their morphology was similar to those formed in the common stem cell assay. Cloning efficiency and colony size depended on the mean pore diameter of the glass membrane, with best colony growth within tubes with a pore diameter ranging from 8.5 nm to 14 nm. A linear relationship between number of cells seeded and number of grown colonies could be demonstrated for the cell lines MDA-231 and Colo 201. Colony growth achieved within porous glass capillary tubes is comparable to that achieved in Petri dishes and in nonporous tubes. We conclude that the porous capillary cloning system meets the basic suppositions for a quantitative cloning assay. Moreover, the porosity of the glass membrane offers the possibility of variable perfusion of medium and drugs. Further investigations will focus on various perfusion modalities and chemosensitivity testing.

Animals↗
PubMed1992

Experimental animal model for the evaluation of chemotherapeutical effects on osteosarcoma.

In previous studies radiation-induced osteosarcoma transplanted onto nude rats has been shown to have an extraordinary similarity to human osteosarcoma. In this report the effects of a standard chemotherapeutic regimen on this experimental bone tumor are described. Examination of the histology and of the water content of the tumor confirmed that a high-dose cyclophosphamide monotherapy can cause severe necrosis in the tumor and its seeded lung metastases. A significant decrease in tumor volume of 50% (p < or = 0.01) was provoked and increased the mean survival rate of the treated rats (untreated rats: mean = 39.3 days) significantly to 53.6 days after transplantation of tumor fragments (p < or = 0.01).

Animals↗
PubMed1991

Kinetics of water sorption in packaging materials for food.

The water content of paper and its time dependence are of great importance for the use of paper and cardboard as packaging materials. The physical process of water sorption and the mechanisms of water "binding" in paper, as fundamental principles of the kinetics, are discussed. Water exists in up to four different "states" (i.e. domains of mobility) in paper: the first layer at the primary sites on the surface of the fibers; the multimolecular layers, with less "binding" energy, on these inner surfaces; condensed water in the voids; and dissolved water in the cellulose fibers. All these "states" influence the shape of the sorption isotherm and correspond to a different water content and to different transport mechanisms. The various types of water "binding" on paper were studied by measuring the transversal relaxation rate, T2, using a pulsed Nuclear Magnetic Resonance spectrometer (minispec pc 120). In addition, a non-destructive, fast method of determining the water content in packaging materials with NMR spectroscopy is described.

Adsorption↗
PubMed1982

Urethral plug--a new secondary male sex characteristic in rat and other rodents.

The plug is an eosinophilic mass, partly homogenous and partly porous, filling the proximal urethra in rats and occasionally extending into the bladder. Its average weight in 131 adult rats was 0.063 g. These plugs are normally present in the urethra of adult male rats, and this seems to be the case for all laboratory Muridae and Cavidae. The absence of a plug in an adult male may be a sign of abnormality associated with failing health. There is an interesting similarity between the amino acid composition of the content of seminal vesicles, that of the urethral plug, and that of the copulatory vaginal plug in female rodents.

Animals↗
PubMedDate not supplied

Kinetic analysis of androstenedione 5 alpha-reductase in epithelium and stroma of human prostate.

In the human prostate, various androgen-metabolizing enzymes are present. Among these enzymes, testosterone 5 alpha-reductase seems to be dominant. However, androstenedione is also a potential substrate of the prostatic 5 alpha-reductase. To address the question of to what extent the reduction of androstenedione to androstanedione occurs, the present study describes in detail the kinetic characteristics (Km and Vmax) and possible age-dependent alterations of this enzymatic step in epithelium and stroma of the human prostate. In normal prostate (NPR), the mean Km (nM) and Vmax (pmol/mg protein.h) were about twofold higher in stroma (Km, 211; Vmax, 130) than in epithelium (Km, 120; Vmax, 56), whereas in the benign prostatic hyperplasia (BPH), the mean Km (nM; mean +/- SEM) and Vmax (pmol/mg protein.h; mean +/- SEM) were about sixfold higher in stroma (Km, 668 +/- 121; Vmax, 415 +/- 73) than in epithelium (Km, 120 +/- 10; Vmax, 73 +/- 8). In BPH, those differences between epithelium and stroma were highly significant (p < 0.001). However, the efficiency ratios (Vmax/Km) of neither BPH nor NPR showed any significant differences between epithelium (NPR, 0.47; BPH, 0.62 +/- 0.06) and stroma (NPR, 0.70; BPH, 0.63 +/- 0.05). With respect to age-related changes, only stroma showed a significant increase of Km (p < 0.01) and Vmax (p < 0.05) with age. In summary, in both epithelium and stroma of the human prostate, a 5 alpha-reductase converts in measurable amounts androstenedione to androstanedione. The kinetic data were, in part, different between epithelium and stroma; the reason for this difference remains unclear. In comparison to other metabolic conversions, such as testosterone to dihydrotestosterone and androstenedione to testosterone, it is unlikely that, in the human prostate, the adrenal androgen androstenedione contributes significantly to the formation of testosterone and, further, of dihydrotestosterone.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗