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P Schulz

Publications and source records attributed to P Schulz.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Autocrine growth mechanisms of cholesteatoma epithelium].

Transforming growth factor alpha (TGF alpha) and interleukin 1 alpha (IL-1 alpha) are known to be produced by normal human keratinocytes stimulating their proliferation. The distribution and expression of TGF alpha and IL-1 alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody against TGF alpha and a polyclonal one against IL-1 alpha. Normal retroauricular skin was stained for comparison. Staining for TGF alpha was consistently stronger in cholesteatoma epithelium than in normal epidermis, and encompassed all epithelial cell layers. Immune cells occurring in the stroma of cholesteatoma also reacted positively for TGF alpha. The intensity of staining for IL-1 alpha was markedly stronger in cholesteatoma tissue than in normal epidermis. All cellular layers of the squamous epithelium of cholesteatoma stained strongly and uniformly for IL-1 alpha, whereas the keratin layer was negative for IL-1 alpha. In the connective tissue beneath the cholesteatoma epithelium intensely positive cells were scattered between negative stromal cells. These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF alpha and IL-1 alpha as well as with a paracrine stimulation by immune cells. Both factors contribute to the unrestrained growth of cholesteatoma in the middle ear cavity.

Cell Division↗
PubMed1993

Aberrant expression of epidermal growth factor receptor in aural cholesteatoma.

A monoclonal antibody recognizing an epitope of the external domain of the human epidermal growth factor (EGF) receptor was used in an alkaline phosphatase-antialkaline phosphatase (APAAP) technique to compare the distribution of this protein in normal human skin and aural cholesteatoma. EGF receptors appear to be highly expressed on the basal layer of the epidermis, in hair follicle apocrine sweat glands, and in the capillary system of normal skin. Cholesteatoma epithelium showed increased positive reactions in the suprabasal layers. A heterogeneity in the expression was found in different parts of the cholesteatoma. These results suggest the presence of an aberrant regulation and persistence of EGF receptors in cholesteatoma and confirm the hyperproliferative character of the cholesteatoma epithelium.

Alkaline Phosphatase↗
PubMed1993

Transfer of carbetocin into human breast milk.

OBJECTIVE: To study the transfer of carbetocin into human breast milk. METHODS: Five healthy nursing women, 7-14 weeks postpartum, emptied their breasts using a breast pump and then received 70 micrograms carbetocin by intramuscular injection. Using a radioimmunoassay, the concentrations of carbetocin were measured in plasma and breast milk samples obtained before carbetocin administration and at 15, 30, 60, 90, 120, and 240 minutes after drug administration. RESULTS: For plasma, the mean (+/- standard deviation) area under the curve (AUC) of carbetocin versus time was 1119.3 +/- 315.9 pg/mL, a value about 50 times higher than the mean AUC for carbetocin in breast milk (18.6 +/- 13.7 and 29.0 +/- 23.8 pg/mL for the right and left breast, respectively). The ratio of milk to plasma AUC was low: 1.7 +/- 0.9 and 3.1 +/- 2.8% for the left and right breast, respectively. No serious adverse reactions occurred and no clinically significant changes in vital signs were found. CONCLUSION: Very little carbetocin is transferred into human breast milk, presenting little risk to breast-fed infants.

Adult↗
PubMed1993

Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.

Human cDNA clones encoding four novel putative transmembrane protein serine/threonine kinases, denoted activin receptor-like kinase (ALK) -1, -2, -3 and -4, were obtained using a polymerase chain reaction (PCR)-based strategy. The PCR primers were designed based upon the sequence similarity between the activin receptor type II and Daf-1. The cDNA clones for ALK-1, -2 and -3 encode complete proteins of 503, 509 and 532 amino acids respectively. The ALK-4 cDNA is incomplete and the predicted protein of 383 amino acids has a truncated extracellular domain. The ALKs share similar domain structures, comprising predicted signal sequences at the N-terminals, followed by hydrophilic cysteine-rich ligand-binding domains, single hydrophobic transmembrane regions and C-terminal intracellular portions that consist almost entirely of putative serine/threonine kinase domains. The ALKs have approximately 40% sequence identity to activin receptors type II and IIB, transforming growth factor-beta (TGF-beta) type II receptor and Daf-1 in the kinase domains. However, the sequence identities are higher (60-79%) between ALK-1, -2, -3 and -4, suggesting that they form a subfamily among the putative receptor serine/threonine kinases. The extracellular domains of ALKs show only little sequence identity to other putative receptor serine/threonine kinases, but the cysteine residues are conserved. Their structural properties suggest that ALK-1 to -4 are receptors that may bind ligands that are members of the TGF-beta superfamily. The expression of mRNA in human tissues varied for the different ALKs; ALK-2 and ALK-4 showed ubiquitous tissue expression patterns, whereas the distribution of ALK-1 and ALK-3 varied strongly between different tissues with more restricted expression patterns. These results suggest that each ALK may have different in vivo functions.

Activin Receptors↗
PubMed1992

Scale-up of recombinant protein purification by hydrophobic interaction chromatography.

The scale-up of hydrophobic interaction chromatography is described. Human recombinant superoxide dismutase was used as a model. The scale-up was performed by keeping the height to diameter (H/D) ratio of the column constant. The success of scale-up was evaluated by reversed-phase high-performance liquid chromatography of the eluted material. The wrong H/D ratio causes decreased resolution.

Chromatography, High Pressure Liquid↗
PubMed1992

Identification of gram-negative bacteria by isoelectric focusing of soluble cellular proteins.

Strains of Escherichia coli, Pseudomonas aeruginosa and Proteus mirabilis, isolated from clinical specimens were disrupted by repeated freezing in liquid nitrogen and thawing at room temperature. The samples were separated by isoelectric focusing using polyacrylamide gels. The resulting protein patterns showed clear differences between the three species and made identification possible.

Bacterial Proteins↗
PubMed1992

Immunotype findings in macrophages in aural cholesteatomas.

Since a heavy cellular infiltrate is seen in the stroma of most aural cholesteatomas, we attempted to characterize this cell population in more detail using monocyte/macrophage-specific monoclonal antibodies. KiM1 + (specific for CD11c antigen, the 150 kDa alpha-chain of a leukocyte integrin), and KiM6+ phagocytes were present in two- or fourfold higher numbers in the stroma of the six excised cholesteatomas than in the control tissues. Since the stroma of the cholesteatoma is devoid of microvessels, the typical perivascular localization of dermal macrophages was not seen in the cholesteatomas studied. The density of the macrophages in the normal ear skin was much higher in the upper dermis than in the lower dermis. In the cholesteatomatous specimens, the phagocytes were evenly scattered within the connective tissue and the cellular infiltrate. In contrast to diseased skin, no Mac 387+ macrophages were detected in the cholesteatomas. A great number of phagocytic cells closely resembling dermal macrophages was found in the stroma of the cholesteatomas and probably contributes to an active autoimmune process.

Antibodies, Monoclonal↗
PubMed1992

Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone.

The mechanism of down-regulation of c-myc RNA associated with androgen-induced suppression of the transformed phenotype in the human prostate carcinoma cell line LNCaP was investigated. The synthetic androgen mibolerone (7 alpha-17 alpha-Dimethyl-19-nortestosterone) reversibly inhibits the proliferation of LNCaP cells and, from 12-72 h after hormone addition reduces the level of c-myc transcripts to a few per cent of controls. P1, P2, and P0 c-myc transcripts decline at the same rate, whereas P3 transcripts are much less hormone sensitive. Nuclear run-on analysis revealed that c-myc is down-regulated at the level of transcription initiation in LNCaP cells. The level of c-myc transcripts prevailing in untreated control cells can be restored in androgen-induced cells by excess antiandrogen, indicating the involvement of the androgen receptor in c-myc down-regulation.

Blotting, Northern↗
PubMed1992

Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus.

Carbetocin, a long-acting oxytocin analog, was administered by intravenous and intramuscular injection to 40 women 24 to 48 hours postpartum. Intravenous injection of 8 to 30 micrograms produced a tetanic uterine contraction within 2 minutes, lasting about 6 minutes, followed by rhythmic contractions for a further 60 +/- 18 minutes. Intramuscular injection of 10 to 70 micrograms also produced tetanic contraction in less than 2 minutes, lasting about 11 minutes, and followed by rhythmic contractions for an additional 119 +/- 69 minutes. The prolonged duration of activity after intramuscular compared with the intravenous carbetocin was significant (p = 0.020). Carbetocin produced mild lower abdominal cramping in most patients and severe pain in three patients who received 50 or 100 micrograms intravenously or 70 micrograms intramuscularly. Approximately half of the patients also experienced flushing and warmth. Although carbetocin has not yet been studied immediately postpartum, its prolonged uterine activity suggests that carbetocin may offer advantages over oxytocin in management of the third stage of labor.

Adult↗
PubMed1992

[Hyperproliferation-associated keratin 16 expression in cholesteatoma].

The position of a cell in a stratified squamous epithelium correlates with its state of differentiation as well as with the expression of certain cytokeratins. By means of both immunohistochemistry using the APAAP method and high resolution one-dimensional gel electrophoresis, specimens of cholesteatoma epithelium and normal ear skin were investigated whether they contain keratin 16 (K 16) which is known to be a marker of hyperproliferation. It could be shown that K 16 is expressed in all layers of cholesteatoma epithelium. Further to prove this fact gel electrophoresis was used showing a protein band at the localization of keratin 16. Hence, cholesteatoma can be seen as a locally hyperproliferative disease.

Cell Division↗
PubMed1992

Transcriptional regulation of prostate kallikrein-like genes by androgen.

Using gene-specific synthetic oligonucleotides the expression and regulation of kallikrein-like genes in the human prostatic cancer cell line LNCaP were studied. Prostate-specific antigen (PSA) and human glandular kallikrein (hGK-1) together constitute a subfamily of serine proteases exclusively produced in the human prostate. RNA analysis revealed that both genes are expressed in LNCaP cells with PSA basal levels being 2-fold higher than hGK-1 levels. Both mRNAs are induced over a period of 24 h in the presence of 3.3 nM of the synthetic androgen mibolerone. Stimulation of PSA RNA is about 5-fold, whereas hGK-1 stimulation is less pronounced. Nuclear run-on analysis revealed that androgen induction of kallikrein-like genes in LNCaP cells is a rapid event (less than 3 h) occurring at the level of transcription initiation. Treatment of cells with cycloheximide demonstrates that, while PSA/hGK-1 basal transcription strictly depends on continuous protein synthesis, transcriptional induction by androgen does not. This suggests the direct involvement of the androgen receptor in the induction process independent of additional labile protein factors necessary for kallikrein basal transcription. A binding motif is present in the PSA and hGK-1 promoters, closely resembling the consensus sequence for steroid-responsive elements. The androgen antagonist cyproterone acetate was also able to stimulate transcription of kallikrein-like genes in LNCaP cells. In contrast, androgen-dependent transcriptional suppression of the protooncogene c-myc was strongly counteracted by cyproterone acetate. Thus, antiandrogens act differentially on androgen-regulated prostate-specific (PSA, hGK-1) and growth-related (c-myc) gene expression in LNCaP cells.

Androgen Antagonists↗
PubMed1992

[Conservative, palliative therapy of malignant pleural mesothelioma].

No effective conventional therapy for malignant pleural mesothelioma has yet been described. Radiotherapy does not increase median survival, but there is a palliative analgesic benefit. Chemotherapy with a different regimen in 182 patients led to a median survival time of 12 months. In comparison to an untreated historical group of 142 patients, there is an advantage in survival of 5 months. Additional surgical treatment has not prolonged the life expectancy. The percentage of long-time survivors was 5.5%.

Adult↗
PubMed1992

Possible role of interleukin 1 alpha and interleukin 1 beta in the pathogenesis of cholesteatoma of the middle ear.

Cholesteatoma of the middle ear is characterized by the presence of hyperproliferative keratinizing squamous epithelium in the middle ear cavity and destruction of adjacent bone. Interleukin 1 (IL-1) is an autocrine growth factor for normal keratinocytes and is capable of inducing bone degradation. The distribution of two molecular species of IL-1, IL-1 alpha and IL-1 beta, was investigated immunohistochemically in the hyperproliferative epithelium of cholesteatoma, in normal epidermis of the auditory canal and of the retroauricular region, and in nonkeratinizing tonsillar epithelium. In all squamous epithelia examined, IL-1 alpha and IL-1 beta were present in comparable amounts. The IL-1 content of cholesteatoma epithelium was clearly increased in relation to normal skin keratinocytes. All cellular layers of cholesteatoma epithelium stained strongly and uniformly for Il-1 alpha and IL-1 beta, whereas the keratin layer was negative for IL-1. No particularly strong reaction with basal cells was detected. In the connective tissue under the squamous epithelium of cholesteatoma, intensely positive cells were scattered between negative stromal cells. Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-macrophage lineage, stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, and contribute to the enhancement of bone destruction in the presence of cholesteatoma.

Cholesteatoma↗
PubMed1991

Synthetic androgens suppress the transformed phenotype in the human prostate carcinoma cell line LNCaP.

Experiments have been designed to investigate hormonal effects on the human prostatic carcinoma cell line LNCaP in the presence of complete foetal calf serum. At physiological concentrations (3.3 x 10(-9)M), several derivatives of 17 alpha-methyl-testosterone led to a significant reduction of cell proliferation, inhibition of colony formation in soft agar, change of morphology, induction of a prostate specific mRNA and down-regulation of c-myc RNA. Two different antiandrogens, hydroxyflutamide and cyproterone acetate, were capable of reversing the effects exerted by the synthetic androgens on growth properties. The proliferation rate of control cells devoid of androgen receptor was not inhibited by synthetic androgens. Our results indicate that the cellular androgen response mechanism of LNCaP cells is intact and that synthetic androgens elicit androgen receptor mediated suppression of the transformed phenotype. Rare cases of remission of prostatic cancer on androgen treatment have been reported. LNCaP cells may be a model of an uncommon class of prostatic cancer which responds favourably to androgen treatment.

Antigens, Neoplasm↗
PubMed1991

[Longitudinal study of colophony exposed workers and control probands].

267 solderers and 239 controls from a cross-sectional study were reexamined after a five-year period. Thereby the correlation between prevalences of respiratory symptoms and work-place concentrations of solder flux fume was confirmed. The follow-up of lung function revealed a higher influence of smoking habits compared to occupational exposures. The MBTH-method is suitable for estimation of exposure, if smoking and other aldehyde sources are excluded.

Adult↗
PubMed1990

Role of the mitochondrial bc1-complex in the cytotoxic action of diethylstilbestrol-diphosphate toward prostatic carcinoma cells.

In previous work (P. Schulz et al., Cancer Res., 48: 2867-2870, 1988) we have demonstrated that diethylstilbestrol (DES), DES-monophosphate, and DES-diphosphate (DESDP) are generally cytotoxic at concentrations attained in patients' sera during therapeutic DESDP infusions for progressed carcinoma of the prostate. We have extended this work and addressed two questions: (a) Is DESDP itself a completely nontoxic prodrug which has to be transformed into the active species DES by a phosphatase? (b) Which metabolic or regulatory mechanism in a cell is the target of DES action? Using cell cultures in phosphatase-depleted media we could provide evidence that DESDP exerts cytotoxic activity only after conversion to DES. Oxygen electrode experiments and difference spectra with intact mitochondria demonstrated that DES did not act as an uncoupler, but inhibited electron flow from ubiquinone to cytochrome c1. Phenomena previously observed in DES-treated cells could be explained by distortion of the energy metabolism.

Acid Phosphatase↗
PubMed1990

Inositol monophosphate esterase inhibition by lithium in normal human studies using neuroendocrine tests. Part I. PRL and TSH responses to TRH.

1. Many neuroendocrine events are mediated by intracellularly second messengers, among which are the breakdown of phosphatidylinositol 4,5-biphosphate (PIP2). 2. Lithium (Li) was shown in therapeutic doses to be a specific inhibitor of the enzyme inositol monophosphate esterase Li reduces the turnover of PIP2 and diminishes the cell responses. 3. In order to investigate this new mode of action of Li the authors studied the influence of acute dose of Li on the response of prolactin (PRL) and thyrotropin (TSH) to thyrotropin stimulating hormone (TRH), a stimulation mainly mediated through the activation of the turnover of PIP2. 4. In seven normal subjects a single dose of 19.80 meq of Li reduced the response of PRL in 4, and augmented it in 3 subjects: Li decreased the TSH response in 4 subjects, it was increased in 1 and remained unchanged in 2. 5. These results are discussed in the light of the different interactions between hormone secretion, and the fact that adenopituitary is located out of the brain blood barrier.

Adult↗