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Biomedical subjects

U Stein

Publications and source records attributed to U Stein.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differential expression of the pS2 protein in the human prostate and prostate cancer: association with premalignant changes and neuroendocrine differentiation.

The distribution of the estrogen inducible pS2 protein was investigated in benign and malignant prostate tissue by the avidin-biotin complex method. Prostate tissue obtained from 20 patients without clinical and histological evidence of malignant disease consistently lacked pS2 immunoreactivity. Conversely, nonneoplastic tissue from 36 total prostatectomies with locally advanced prostate cancer showed a variable degree of pS2 reactivity in normal or hyperplastic glands and in prostatic intraepithelial neoplasia (PIN) adjacent to the cancerous lesions. This suggests that the pS2 gene expression detected in nonmalignant tissue may be related to early premalignant changes of prostate glands harboring significant carcinomas. In prostate cancer the pS2 protein was detected in close association with neuroendocrine (NE) differentiation as assessed by Chromogranin A (Chr A) immunoreactivity. Double labeling techniques showed that pS2 immunoreactivity recognizes both endocrine (Chr A-positive) and adjacent exocrine (Chr A-negative) cell types within NE foci. Whereas pS2 expression was consistently confined to NE differentiation in untreated tumors, carcinomas that relapsed after hormonal therapy showed increased pS2 immunoreactivity, even in the absence of NE features. The differential expression of the pS2 peptide in nonneoplastic tissue from patients with and without malignant disease indicates that pS2 immunohistochemistry may be useful in the diagnostic evaluation of negative biopsy specimens. Furthermore, the results suggest that the immunohistochemical spectrum of pS2 in prostate cancer may include endocrine differentiated and presumably related cell populations.

Carcinoma↗
PubMed1995

Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells.

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has potential prognostic and therapeutic implications. In a recent study we were able to provide immunohistochemical evidence that endocrine-paracrine cell types represent an androgen-insensitive cell population in prostate cancer, documented by the consistent lack of the pertinent receptor. In this study we investigated the proliferative activity of endocrine-paracrine cell types in normal, hyperplastic, and neoplastic prostate tissue. Using double-label techniques for the endocrine marker chromogranin A (chr A) and the proliferation-associated MIB-1 antigen, we evaluated the proliferative status of endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma showing marked NE differentiation. In this series of carcinomas and in nonneoplastic tissue the proliferative activities were exclusively restricted to nonendocrine cell populations, whereas endocrine-paracrine cell types characterized by Chr A consistently lack MIB-1 immunoreactivity. This may indicate that prostatic endocrine-paracrine cell types do not participate in the cell cycle during normal, hyperplastic, and neoplastic prostatic growth. Based on the present information, the endocrine phenotype can be considered to be an androgen-insensitive, postmitotic subpopulation in the prostate and prostate cancer.

Adenocarcinoma↗
PubMed1994

The proliferative function of basal cells in the normal and hyperplastic human prostate.

To obtain more insight into the proliferative function of basal and secretory cell types in human prostate, we studied the immunoprofile of three well-characterized proliferation-associated antigens (Ki-67, PCNA, MIB 1) in normal and hyperplastic prostate tissue. Distinction between labeled basal and secretory cell types was made by simultaneous demonstration of the proliferation-associated antigens and basal cell-specific cytokeratins in identical sections. In normal and hyperplastic acini, approximately 70% of labeled cells were of the basal cell phenotype. These data clearly suggest that the proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. Compared to normal and hyperplastic conditions, severe proliferative abnormalities were detected in high-grade prostate intraepithelial neoplasias (PIN), as documented by the extension of the proliferative compartment up to the luminal border. Conversely, approximately 70% of proliferating cells detected in atypical hyperplasias that progressed in invasive carcinomas were localized in the remaining basal cell layer. These findings may indicate the proliferative role of basal cells in the epithelial renewal, and the development of hyperplastic and neoplastic disorders in the human prostate.

Antibodies, Monoclonal↗
PubMed1994

Influence of cytokines on mdr1 expression in human colon carcinoma cell lines: increased cytotoxicity of MDR relevant drugs.

We investigated the effects of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma and interleukin-2 (IL-2) on the mdr1 gene expression in four human colon carcinoma cell lines (Lo Vo, HT 115, SW 480, and LS 174T) at different times (8, 24, 48, and 72 h). We found no significant changes in mdr1 expression after 8 h and 24 h of cytokine treatment in all four lines. After 48 h and 72 h, however, a marked reduction of mdr1 expression in Lo Vo, HT 115, and SW 480 cells and an unaffected expression in LS 174T cells was observed. We examined whether the cytokine-mediated reduction of mdr1 expression correlates to the multidrug resistance (MDR) phenotype. In those cell lines showing a decreased mdr1 expression after a long-term cytokine pretreatment we found a dramatic enhancement of cytotoxicity of the MDR relevant drugs vincristine and doxorubicin, whereas LS 174T cells remained resistant. By contrast, the simultaneous application of cytokines and cytostatics caused no additive or synergistic effects. We conclude that in certain colon carcinoma cell lines a decreased mdr1 expression caused by prolonged cytokine pretreatment correlates with an enhanced cytotoxicity of drugs susceptible to MDR as an MDR-overcoming effect.

Antineoplastic Agents↗
PubMed1994

Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers.

The prostatic epithelium is composed of three distinct cell populations: secretory luminal, basal, and endocrine-paracrine cells. It is currently unknown whether these basic epithelial cell types are related in a hierarchical pathway of differentiation or are independent and separate entities. In the present study we used double-label techniques for cell-specific markers to search for multidirectional differentiation in normal, hyperplastic, and neoplastic prostate tissue. In normal and hyperplastic conditions subsets of basal cells revealed synchronous expression of basal cell-specific cytokeratins and the prostate-specific antigen, indicating intermediate differentiation between basal and secretory luminal cell types. Furthermore, endocrine-paracrine cells of the closed type focally showed simultaneous expression of chromogranin A and basal cell-specific cytokeratins. These findings highlight the phenotypic plasticity of the basal cell layer in the human prostate. In prostatic adenocarcinoma co-expression of exocrine (prostate-specific antigen) and endocrine (chromogranin A) markers was detected frequently in subsets of malignant cells. Conversely, this amphicrine phenotype was rarely found in hyperplastic glands. The occurrence of multidirectional differentiation within the prostatic endocrine cell system may indicate that endocrine-paracine cells derive from pluripotent stem cells of endodermal origin. Furthermore, the phenotypic plasticity of basal cells suggests that this epithelial compartment houses stem cell populations that give rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic human prostate.

Adenocarcinoma↗
PubMed1994

Point mutations in the mdr1 promoter of human osteosarcomas are associated with in vitro responsiveness to multidrug resistance relevant drugs.

Among human sarcomas, osteosarcomas usually display high intrinsic mdr1 expression while malignant fibrous histiocytomas (MFH) do not. A comparative polymerase chain reaction (PCR)-based sequence analysis of the mdr1 promoter revealed point mutations in seven out of nine osteosarcomas at nucleotides +103 (2 cases T-->C) and +137 (5 cases G-->T). No changes were seen in eight MFHs. When COS cells transfected with CAT constructs containing the T-->C chloramphenicol acetyltransferase mutant mdr1 promoters were treated with vincristine or doxorubicin, expression of the CAT gene was enhanced to a higher extent than with constructs containing wild-type or G-->T-mutant mdr1 promoters. We suggest that there is a correlation between the type of mdr1 promoter mutation and responsiveness to MDR relevant drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Prognostic criteria for initial success in PTA and catheter thrombolysis].

The preliminary results of 1063 percutaneous dilatations (PTA) of iliac or femoropopliteal arteries were evaluated in order to establish pre-existing clinical or morphological criteria with possible influence on the early success rate. Early failure was defined as the impossibility to eliminate the arterial occlusion or re-occlusion within 48 hours. Regarding the clinical criteria the combination of long duration and advanced stage of the disease unfavourably influenced the primary success rate (failure rate of 40%). Morphological factors such as length of occlusion over 10 cm, poor run-off or existence of large arterio-venous shunts had an even worse influence on the early success rate (failure rate of 50-60%).

Angiography, Digital Subtraction↗
PubMed1993

Androgen receptor status in endocrine-paracrine cell types of the normal, hyperplastic, and neoplastic human prostate.

Neuroendocrine differentiation is a frequent occurrence in common prostatic adenocarcinomas and may have prognostic implications in prostatic malignancies. In the present study, we used immunohistochemical double label methods to evaluate the nuclear androgen receptor (AR) status in endocrine-paracrine (EP) cells of normal, hyperplastic, and neoplastic prostate including tumours that recurred after hormonal and radiation therapy. In normal and hyperplastic glands, EP cells characterized by the panendocrine marker chromogranin A (Chr A) did not reveal AR-positivity. This may indicate that prostatic EP cells represent an androgen-independent cell population whose regulatory functions are not influenced by circulating androgens. Unequivocal co-expression of Chr A and AR was very rarely detected in subsets of endocrine differentiated tumour cells in treated and untreated specimens. The widespread absence of nuclear AR in neuroendocrine tumour cells suggests that this phenotype belongs to those cell clones in prostate cancer which are initially androgen-independent and refractory to hormonal therapy.

Adenocarcinoma↗
PubMed1993

Differential expression of alpha 6 and alpha 2 very late antigen integrins in the normal, hyperplastic, and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands.

The very late antigens (VLAs) are alpha beta-heterodimeric transmembrane proteins that include surface cell receptors for laminin (VLA-6) and collagen (VLA-2), which mediate cell-matrix and cell-cell adhesion. We investigated the distribution of VLA-6 (alpha 6, beta 1) and VLA-2 (alpha 2, beta 1) proteins in normal, hyperplastic, and neoplastic human prostate tissue and lymph node metastases by the avidin-biotin complex method. In normal and hyperplastic glands we observed two staining patterns that differed according to the density of alpha 6- and alpha 2-receptors at the site of co-expression with their corresponding ligands (laminin, type IV collagen) in acinar basement membranes (BMs). Band-like deposits with high receptor density suggested strong anchorage of the prostate epithelium to acinar BMs, whereas the absence of this pattern most probably reflected reduced cellular attachment. Very late antigen-6 immunoreactivity showed the band-like pattern in approximately 70% of normal and hyperplastic glands compared with VLA-2, which showed the same pattern in only 5% of cases. In prostatic adenocarcinoma the band-like pattern significantly decreased with dedifferentiation and was consistently absent in grade III lesions. Compared with staining intensities in normal and hyperplastic conditions, grade I and II tumors maintained or overexpressed the VLA-6 receptor in 85% of cases, whereas the VLA-2 receptor was downregulated in approximately 70% of cases. Grade III tumors were characterized by a heterogeneous expression of VLA-6 and VLA-2 proteins, but frequently upregulated their receptors in corresponding lymph node metastases. Regardless of the staining intensity, all primary and metastatic carcinomas investigated expressed VLA-6 and VLA-2 receptors whose extracellular domains were extensively co-expressed with their ligands in neoplastic BM formations. These findings suggest that VLA-6 and VLA-2 receptors mediate attachment of tumor cells to neoplastic BM material, which, in turn, may endow these cells with an increased ability to invade the extracellular matrix.

Adenocarcinoma↗
PubMed1993

Expression of the mdr1 gene in bone and soft tissue sarcomas of adult patients.

The expression of the mdr1 gene was evaluated at the RNA level by northern and slot blot analysis, and at the protein level by immunohistochemistry, in a total of 29 bone and 32 soft tissue sarcomas. All patients, mainly adults, had not received previous chemotherapy. Of the tumours investigated, 69% were mdr1-positive. An intermediate mdr1 expression was observed most frequently, with the exception of osteosarcomas (high) and malignant fibrous histiocytomas (low). Detection of P-glycoprotein in selected tumours revealed consistent results. However, no conclusion can be drawn as yet regarding correlation of mdr1 expression and drug resistance in patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Comparison of the effects of losigamone and its isomers on maximal electroshock induced convulsions in mice and on three different patterns of low magnesium induced epileptiform activity in slices of the rat temporal cortex.

Losigamone (AO-33) is a recemate of a tetronic acid derivative. The effects of losigamone and its three isomers (AO-242, AO-294 and AO-23) were compared on maximal electroshock (MES) induced convulsions in mice and on different patterns of extracellularly recorded, low Mg2+ induced epileptiform activity in slices of the rat temporal cortex. Lowering Mg2+ induced recurrent short discharges in areas CA3 and CA1 while ictaform events that lasted for many seconds were induced in the entorhinal cortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the entorhinal cortex changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. Afterdischarges and interictal events were absent. 50 microM AO-242 showed a similar efficacy to 50 microM AO-33 in reducing and blocking epileptiform discharges in areas CA1 and CA3 while 50 microM AO-294 and 50 microM AO-23 had weaker effects than 50 microM AO-33. Concentrations of 50 microM and 100 microM AO-242 showed a similar efficacy to AO-33 on ictaform events in the entorhinal cortex. Late recurrent discharges were also blocked by AO-33 and AO-242 although at higher concentrations (300 microM). The in vitro observations are with respect to order of efficacy in accordance with the in vivo data obtained in the maximal electroshock test in mice. The order of potency in the MES test was AO-242 greater than AO-33 much greater than AO-294 much greater than AO-23.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Spontaneous splenic rupture in chronic pancreatitis].

A 50-year-old woman complained of upper abdominal pain for several weeks, getting worse and radiating towards the left shoulder in the 24 hours preceding her hospital admission. Plain X-ray film of the abdomen revealed plaque-like calcifications projecting onto the tail of the pancreas. Ultrasound imaging demonstrated splenic rupture with free intra-abdominal fluid. During an emergency laparotomy the spleen was removed. At first the postoperative course was uneventful. But epigastric pain recurred a few days after discharge. Serum amylase and lipase concentrations were elevated (280 U/l and 553 U/l, respectively). Endoscopic retrograde cholangiopancreatography revealed chronic pancreatitis with a 3 cm pseudocyst in the tail of the pancreas. A papillotomy was performed, after which the symptoms rapidly regressed and the pancreatic enzyme concentrations fell. This was thus a case of spontaneous splenic rupture associated with previously undiagnosed chronic pancreatitis with inflammatory papillary stenosis and pseudocyst in the pancreatic tail.

Abdominal Pain↗
PubMed1991

Losigamone.

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Animals↗
PubMed1990

Induction kinetics of delayed fluorescence of sun and shade leaves of Fagus sylvatica in the ms-range.

Induction kinetics of luminescence (= delayed chlorophyll fluorescence or delayed light emission) were measured with sun and shade leaves of a tall beech tree (Fagus sylvatica 'pendula', weeping beech). The kinetics detected in the ms-range are contrasted for the upper and the lower leaf side. The influence of the following parameters is demonstrated: time of dark-adaptation prior to the measurement, intensity of the excitation light and photoinhibitory treatment. The effects are discussed with respect to chlorophyll concentration, absorption of the excitation light, reabsorption of the luminescence and photosynthetic activity of the leaf tissue. It is shown that the luminescence signal and its kinetic are determined mainly by the properties of the mesophyll parenchyma facing the detector. Thus the more densely packed palisade parenchyma at the upper leaf side exhibits a lower luminescence and a slower kinetic than the spongy parenchyma at the lower leaf side, which is characterized by many aerial interspaces. Our study shows that luminescence kinetics can be applied to interpret the physiological state of a specific leaf tissue. They may serve as an indicator of disorders in the photosynthetic function.

Kinetics↗