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P Hofer

Publications and source records attributed to P Hofer.

At least 19 recordsLinked to original sources
PubMed1995

Neu differentiation factor/heregulin modulates growth and differentiation of HC11 mammary epithelial cells.

The HC11 mouse mammary epithelial cell line has proven to be a valuable in vitro model to study the roles of peptide factors and hormones involved in the growth and differentiation of mammary cells. Treatment of HC11 cells with the lactogenic hormones, dexamethasone, insulin, and PRL (DIP), leads to cellular differentiation and production of the milk protein beta-casein. We have analyzed the effects of Neu differentiation factor (NDF)/heregulin, a newly described activating ligand for erbB-2 and other members of the epidermal growth factor (EGF) receptor family, on cell growth and the expression of milk proteins in HC11 cells. In these cells, NDF induces tyrosine phosphorylation of erbB-2 and erbB-3. Both NDF and EGF stimulate HC11 cell proliferation and promote the responsiveness of HC11 cells to lactogenic hormones. NDF induces the expression of a 22-kilodalton milk protein. This protein is up-regulated by other factors, including dexamethasone, EGF, and basic fibroblast growth factor, and is controlled in a manner distinct from that of beta-casein. Like EGF, NDF inhibits the DIP-induced expression of beta-casein at the level of transcription. The inhibition is due to the negative effect of NDF on the activation of mammary gland factor (MGF/Stat5), a member of the Stat family of transcription factors, which is essential for beta-casein gene expression.

Animals↗
PubMed1992

Overexpression of the glucocorticoid receptor represses transcription from hormone responsive and non-responsive promoters.

The glucocorticoid receptor (GR) is a regulable transcription factor which can bind to DNA response elements in the vicinity of inducible gene promoters and enhance the rate of transcription initiation. The concentration of endogenously expressed GR has been shown to limit the magnitude of the transcriptional induction response in cultured cells. We have investigated the consequence of increased GR expression on the transcriptional activity of a hormone responsive promoter, the MMTV LTR, and on three non-responsive promoters, the RSV LTR, the SV40 early promoter and the c-fos promoter in transiently transfected cells. Low receptor concentrations allow a slight hormonal induction of the MMTV LTR while maximal inducibility can be observed at intermediate GR concentrations. High GR expression reduces the hormonal induction on the MMTV LTR and also adversely effects transcription from the RSV LTR, the SV40 and c-fos promoters. This repression effect is dependent on GR activation. These experiments suggest that the GR interacts with a nuclear factor that is required for the activation of all four promoters. It is probable that "squelching", i.e. protein-protein complex formation in the nucleus leads to the sequestration of interacting proteins(s) essential for the transcription machinery, causing a limitation for the initiation events.

Animals↗
PubMed1992

The influence of the post-Chernobyl fallout on birth defects and abortion rates in Austria.

OBJECTIVES: We analyzed the influence of the radioactive fallout after the Chernobyl disaster on the rate and regional distribution of birth defects and abortion rates in southern Austria. STUDY DESIGN: During 1985 to 1989 a total of 66,743 births was monitored. Twelve sources provided data on 1695 cases of birth defects, 1579 of which were suitable for analysis. All cases were analyzed in terms of their calculated conception date and divided into three main groups according to their vulnerable phase of embryogenesis, spermatogenesis, and oogenesis. To study possible regional changes, the findings were plotted in 17 political subdistricts. The overall abortion rate and the counseling frequency at termination clinics was determined. RESULTS: No significant changes in the incidence of birth defects, abortion rate, or counseling rate at pregnancy termination clinics were observed. CONCLUSIONS: Assessing the teratologic potential of low-dose radiation is difficult and requires adequate grouping of birth defects, sufficient baseline data, and highly reliable registries.

Abortion, Induced↗
PubMed1992

Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as well as local signals cooperate in the in vitro regulation of MGF activity.

Animals↗
PubMed1991

[Experience with plating of intra-articular fractures of the calcaneus].

There have been various attempts to improve the results of treatment of fractures of the calcaneus in recent decades. Descriptions of conservative treatment with plaster cast, functional treatment and several methods of closed and open reduction and stabilization have been published. We believe that, especially in young patients, intraarticular fractures with depression of the posterior articular facet should be treated by open anatomical reduction, autologous bone grafting and stabilization with plates. In our clinic 15 fractures of the calcaneus have been treated in this manner in the last few years, and the results are very satisfying.

Adult↗
PubMed1990

Prolactin and glucocorticoid hormones control transcription of the beta-casein gene by kinetically distinct mechanisms.

Transcription of the beta-casein milk protein gene in the HC11 mouse mammary epithelial cell line is induced synergistically by the hormones glucocorticoid and PRL. Sequential treatment of HC11 cells with glucocorticoid and PRL demonstrated that the two hormones had different modes of action on beta-casein transcription. Pretreatment with dexamethasone enhanced the response to subsequent induction by PRL, but not vice versa. Dexamethasone increased the sensitivity of the cells to respond to PRL. The increase in sensitivity was slow, extended for 16 days, and could be rapidly reversed by withdrawal of dexamethasone. The dexamethasone-induced sensitivity for the rapid transcriptional regulation by PRL could be observed with transfected rat beta-casein promoter-chloramphenicol acetyltransferase constructs retaining only 175 basepairs upstream from the transcription initiation site. Expression of the endogenous mouse beta-casein gene was regulated identically to that of the promoter constructs with respect to the synergy of the hormones and their different kinetics of action. In contrast to the slow induction of sensitivity toward PRL, dexamethasone rapidly induced the transcription of a mouse mammary tumor virus long terminal repeat controlled gene in HC11. This demonstrated a normal transcriptional activation of the glucocorticoid receptor in this cell line. Thus, glucocorticoid may regulate beta-casein gene transcription indirectly, inducing or repressing other glucocorticoid-regulated genes, whereas the interaction of PRL with its receptor causes a rapid induction of the beta-casein gene promoter.

Animals↗
PubMed1990

[Muscle structure and aerobic performance capacity in recruit training school].

The aerobic performance capacity (VO2 max) and muscle ultrastructural composition was analyzed in 18 subjects undergoing basic training in the Swiss army. Three groups were selected based on their sports activity. Group S contained subjects that had a previous systematic background in sports activities and trained regularly at least three times per week. A second group consisted of subjects that had no previous training and were subjected to an additional, individually adjusted endurance exercise (three times per week) for the first 8 weeks of their service period (group T). The control group (C) had no previous training and followed only the regular military duties. VO2 max was found to be significantly higher in group S at the beginning of the military service. However, VO2 max did not change significantly during the service period in any of the groups, Muscle mitochondria showed a significant change (+19%) only in group T. Heart rate recordings indicated that despite "strenuous" military activity, heart rates rarely reached levels sufficient for an increase in aerobic performance capacity.

Adult↗
PubMed1989

[The value of prenatal ultrasound screening exemplified by abnormalities of the urogenital system. Data from the Styrian malformation register 1985 to 1987].

Over a three-year period (1985 to 1987), the number of fetal malformations was entered into Styrian Malformation Register (SMR). The data were compared with those of the Austrian Ministry of Health. The SMR collected 137 cases of urinary tract malformations, but only six appeared in the Health Ministry statistics. This discrepancy resulted from the different data collection methods. Presently only a small percentage of fetal abnormalities is officially registered. Using the example of urinary tract malformations this paper shows the value of prenatal ultrasound screening. Such infants must be treated soon after delivery to avoid progression of parenchymal damage. Ultrasound examinations should not be restricted to pregnant women at defined risk. Registration of all prenatally diagnosed--or missed--malformations is a quality-control measurement and improves prenatal diagnosis.

Austria↗
PubMed1989

A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production.

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.

Animals↗
PubMed1988

The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle.

1. Caffeine (10 mM)-induced relaxation of guinea-pig isolated trachealis was attenuated and converted to a small spasmogenic response on cooling to 22 degrees C. The relaxant response was restored on rewarming to 37 degrees C and was abolished by indomethacin (2.8 microM). Cooling to 22 degrees C in the presence of indomethacin revealed spasmogenic responses to caffeine which were abolished on rewarming to 37 degrees C. 2. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with acetylcholine (ACh, 10 microM). Caffeine (1 or 10 mM), added as each ACh-induced spasm reached equilibrium, transiently augmented but then suppressed the spasm. On cooling from 37 degrees C to 12 degrees C, the increment in spasm evoked by caffeine increased relative to the spasm evoked by ACh. 3. Trachealis treated with indomethacin (2.8 microM) was repeatedly dosed with caffeine (10 mM). At 37 degrees C caffeine had little effect but it caused spasm when the tissue was cooled to 32 degrees C. Spasm amplitude increased as cooling progressed to 12 degrees C. Similar results were obtained with caffeine (1 mM). 4. At 37 degrees C, caffeine, enprofylline, 1,3,7,9-tetramethylxanthinium (TMX), theobromine, theophylline, xanthine and forskolin each caused concentration-dependent suppression of tracheal tone. Among the xanthine derivatives the rank order of potency was enprofylline greater than theophylline greater than caffeine greater than theobromine greater than xanthine greater than TMX. 5. In trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, the xanthines each caused concentration-dependent spasm. The rank order of potency was theobromine greater than or equal to theophylline greater than or equal to caffeine greater than or equal to enprofylline greater than xanthine greater than TMX. Forskolin was devoid of spasmogenic activity. 6. Trachealis treated with indomethacin (2.8 microM) and maintained at 12 degrees C, was repeatedly dosed with either caffeine (10 mM) or potassium chloride (KCl, 40 mM). Caffeine-induced spasm was attenuated in a Ca2+-free medium containing EGTA (2 mM), modestly at first but subsequently more profoundly. KCl did not evoke spasm at 12 degrees C but at 37 degrees C the KCl-induced spasm was virtually abolished at its first trail in the Ca2+-free, EGTA-containing medium. 7. It is concluded that caffeine, other alkylated xanthines and xanthine itself share a spasmogenic action in guinea-pig isolated trachealis which is best observed when the tissue is treated with indomethacin (2.8 microM) and maintained at 12 degrees C. The spasmogenic action represents the release of Ca2+ from intracellular sites of sequestration and may not depend on the intracellular accumulation of cyclic AMP. The rank order of spasmogenic potency of the xanthine derivatives differs markedly from their rank order of potency in suppressing the spontaneous tone of the trachealis observed at 370C. Since, at 12 degrees C, TMX is spasmogenic at concentrations identical to those causing relaxation at 37 degrees C, it is likely that TMX penetrates the cell. The relaxant effects of TMX do not, therefore, indicate that methylxanthine-induced relaxation is mediated by a receptor located on the external surface of the cell.

Acetylcholine↗
PubMed1985

Benzodiazepine antagonist Ro 15-1788 in self-poisoning. Diagnostic and therapeutic use.

Thirteen patients with benzodiazepine overdosage received the specific benzodiazepine antagonist Ro 15-1788. Intravenous administration of 1.5 to 10 mg reversed the central nervous system depression induced by different benzodiazepine compounds within one to two minutes of injection. These case reports indicate that Ro 15-1788 may be an effective tool in the primary management of self-poisoning.

Adult↗
PubMed1984

Activation of acetylcholinesterase by monovalent (Na+,K+) and divalent (Ca2+,Mg2+) cations.

The activation of acetylcholinesterase [EC 3.1.1.7 (AChE)] by monovalent and divalent metal ions has been investigated by kinetic experiments under steady-state conditions (pH-stat method). It has been shown that at low ionic strength the enhancement of the activity by both monovalent and divalent metal ions can be explained as an electrostatic effect. Thereby, enhancement of the concentration of monovalent metal ions (Na+ and K+) acts by reducing the penetration depth of the electric field of carboxylate groups located at the active center whereby divalent metal ions (Ca2+ and Mg2+) act by a complex formation with these charged groups.

Acetylcholinesterase↗
PubMed1981

Acetylcholinesterase kinetics.

Three mechanisms have been suggested to describe the inhibition of acetylcholinesterase (EC. 3.1.1.7) by an excess of acetylcholine. (i) Substrate inhibition occurs through the reaction of acetylcholine with acetylated enzyme. The deacetylation of this ternary complex is supposed to be completely inhibited. (ii) A ternary complex is formed as in (i). However, the deacetylation is not completely inhibited. (iii) A two-site-mechanism is discussed. Acetylcholine binds either to the active site or to the modifier site. Binding to the latter changes the activity of the active site. Steady state treatment was applied to (i)-(iii). A least squares fit led to catalytic parameters. It is demonstrated that mechanism (ii) is the most simple one which can describe satisfactorily the experimental data. Limits for a set rate constants are derived from the catalytic parameters. A numerical integration shows that the steady state approximation may be used even when the mechanisms are rather complex.

Acetylcholine↗
PubMed1979

Structural investigation of biological material in aqueous environment by means of infrared-ATR spectroscopy.

Infrared attenuated total reflection (ATR) spectroscopy may be used to investigate biological material (e.g., membranes, proteins, erythrocytes etc.) under biological conditions provided that adhesion of the sample can be achieved in aqueous environment. Uncharged lipid multilayer model membranes can be attached by hydrophobic interaction when hydrophobic internal reflection plates (e.g., ZnSe, CdTe) are used. However, if an electric field is applied across the membrane, germanium reflection elements would be preferred because of their low electric resistance (approximately 50 omega cm). This material can also be used if cells or proteins are linked chemically to the ATR plate because of the hydrophilic surface which is similar to that of glass and, thus, enables chemical modification by silanization. It has turned out that good adhesion of uncharged and negatively charged model membranes to germanium plates is achieved when they are coated with a monomolecular layer of aminopropylsilane. There is some evidence that erythrocytes remain more stable when adsorbed to a polymerized aminosilane coating (organic silanization) rather than to the corresponding monolayer (aqueous silanization). Negatively charged germanium surfaces have been obtained by succinylation of the aminosilane coating. Furthermore it has been demonstrated that proteins can be bound to the aminosilane coating by means of carbodiimide. Immobilized acetylcholinesterase was still enzymatically active.

Acetylcholinesterase↗