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C Steiner

Publications and source records attributed to C Steiner.

At least 19 recordsLinked to original sources
PubMed1995

Acute rejection of vascular heart allografts by perforin-deficient mice.

To study the role of perforin in cell-mediated graft rejection, vascularized hearts were grafted to perforin-deficient C57BL/6 and control C57BL/6 recipient mice. Fully allogeneic heart grafts (BALB/c) were acutely rejected by both recipients within 6 days. Peritoneal exudate lymphocytes from control mice but not from perforin-deficient mice exhibit a strong alloreactive cytotoxic activity in vitro. Histological analysis of the rejected tissues demonstrated extensive mononuclear cell infiltrates in both recipients. Flow cytometry analysis and immunohistology of graft-infiltrating cells showed similar proportions of lymphocyte subsets (CD8 >> CD4). Collectively, these data indicate that perforin is not essential in the cell-mediated acute rejection of a fully mismatched heart allograft. However, perforin-dependent effector mechanisms appeared to be limiting in the T cell-mediated rejection of heart allografts differing only at a single major histocompatibility complex class I antigen (bm1), because these grafts survived longer (mean 87.8 days) in perforin-deficient than in control mice (mean 31.5 days).

Animals↗
PubMed1994

The immunosuppressant rapamycin blocks in vitro responses to hematopoietic cytokines and inhibits recovering but not steady-state hematopoiesis in vivo.

The immunosuppressive drug rapamycin suppresses T-cell activation by impairing the T-cell response to lymphokines such as interleukin-2 (IL-2) and interleukin-4 (IL-4). In addition, rapamycin blocks the proliferative response of cell lines to a variety of hematopoietic growth factors, including interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and kit ligand (KL), suggesting that it should be a strong inhibitor of hematopoiesis. In this report, we studied the effects of rapamycin on different hematopoietic cell populations in vitro and in vivo. In vitro, rapamycin inhibited the proliferation of primary bone marrow cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in cell-conditioned media. Rapamycin also inhibited the multiplication of colony-forming cells in suspension cultures containing IL-3 plus interleukin-1 (IL-1) or interleukin-11 (IL-11) plus KL. In vivo, treatment for 10 to 28 days with high doses of rapamycin (50 mg/kg/d, orally) had no effect on myelopoiesis in normal mice, as measured by bone marrow cellularity, proliferative capacity, and number of colony-forming progenitors. In contrast, the same treatment strongly suppressed the hematopoietic recovery normally seen 10 days after an injection of 5-fluorouracil (5-FU; 150 mg/kg, intravenously [i.v.]). Thus, rapamycin may be detrimental in myelocompromised individuals. In addition, the results suggest that the rapamycin-sensitive cytokine-driven pathways are essential for hematopoietic recovery after myelodepression, but not for steady-state hematopoiesis.

Animals↗
PubMed1993

Fast chemiluminescent measurement of RNA polymerase activity based on photon counting technology.

A fast and simple assay for T7 RNA polymerase based upon chemiluminescent detection of the synthesized, digoxigenin-labeled RNA on a nylon membrane with anti-digoxigenin coupled alkaline phosphatase and CSPD as substrate is described. Activity of RNA polymerase is determined with high sensitivity by quantifying the emitted light of the microplate-formatted dot-blot membrane with a photon counting microplate luminometer and a specially designed filter adapter. The described method is one example for the application of this new adapter to measure luminescent membrane filters.

DNA-Directed RNA Polymerases↗
PubMed1992

Antihypertensive and metabolic effects of single and combined atenolol regimens.

The antihypertensive and metabolic effects of placebo (PL), a fixed combination of hydrochlorothiazide (25 mg) and triamterene (50 mg) (HCTZ/TRI), atenolol (25 mg) (Atc-25), atenolol (50 mg) (Ate-50) and their combination with HCTZ/TRI given once daily, were tested on 256 patients with mild-to-moderate essential-hypertension. After 3 weeks of PL monotherapy, 43 patients were randomized to PL (group 1), 41 patients to HCTZ/TRI (group 2), 44 patients to Ate-25 (group 3), 42 patients to Ate-50 (group 4), 43 patients to Ate-25/HCTZ/TRI (group 5), and 43 patients to Ate-50/HCTZ/TRI (group 6) in a double-blind parallel design study and were followed for 4 weeks. At the end of week 7, those patients who were randomized to groups 5 and 6 were allowed to continue for an additional 12 weeks, if their arterial pressure was satisfactorily controlled. Complete blood counts, blood chemistries, urinalyses, and electrocardiograms were done initially and during the study. Monotherapy with HCTZ/TRI, Ate-25, and Ate-50 had significant and equal antihypertensive effects compared with placebo. (P less than .01). However, the combination of Ate-25/HCTZ/TRI and Ate-50/HCTZ/TRI resulted in further reduction of arterial pressure with the effect being greatest with Ate-50/HCTZ/TRI (P less than .001). Patient groups 3 through 6 had also slower heart rates compared with groups 1 and 2 (P less than .01). Mild, but statistically significant, increases in BUN, glucose, triglycerides, and uric acid were noted in groups 2, 5, and 6 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗
PubMed1991

Mapping the epitopes of neutralizing anti-human IL-3 monoclonal antibodies. Implications for structure-activity relationship.

The epitopes of neutralizing mAb were mapped in order to identify a receptor binding site on human IL-3 (huIL-3). To initiate this structure and activity analysis, four neutralizing mAb were selected on the basis of preventing rhuIL-3 stimulated proliferation of peripheral blood cells from a patient with chronic myelogenous leukemia (CML). In order to identify continuous epitopes, the neutralizing mAb were assayed in a solid-phase ELISA for their reactivity with either denatured rhuIL-3 or with the peptides generated by digestion of rhuIL-3 by using two different proteinases. Two of the neutralizing mAb recognized single fragments from both digestions. Amino acid (aa) sequence determination showed that these peptides overlap, defining a region of 22 aa (aa 29 to 50 of the mature rhuIL-3 protein). In a competition ELISA, the two continuous epitopes were shown to be linked to one another and to the two discontinuous epitopes, suggesting that all four neutralizing mAb bind to a discrete region of the IL-3 molecule, which might be involved in binding to the IL-3R.

Amino Acid Sequence↗
PubMed1990

Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site.

Silencer elements, by analogy to enhancer elements, function independently of their position and orientation. We show that the chicken lysozyme silencer S-2.4 kb has many other characteristics in common with enhancer elements. The silencer is comprised of modules that independently repress gene activity--repression being increased synergistically when different or identical modules are combined. Repression is effective both on a complete and on a minimal promoter consisting of a TATA box only. One silencer module is bound in vitro by a 75-93 kd protein, termed NeP1; the other can be bound either by the product of the oncogene v-erbA or by the thyroid hormone receptor. This erbA binding site is unusual in that the palindromic sequence is inverted.

Animals↗
PubMed1990

Case study: disease prevention--new roles for nurses in rural Australia.

Nurses are taking a leading role in preventing disease on the North Coast of New South Wales. In addition to heart health programs, nurses are also involved in Early Childhood Clinics, immunization campaigns, pap smear and breast self-exam campaigns, nutrition education and walking-for-pleasure groups. It would be safe to say that without nurses making new roles for themselves, there would be very few disease prevention campaigns on the North Coast.

Community Health Nursing↗
PubMed1989

Cooperative interaction of chicken lysozyme enhancer sub-domains partially overlapping with a steroid receptor binding site.

Expression of the lysozyme gene is a marker for the differentiation of macrophages, lysozyme transcription being gradually increased during maturation. We have analyzed the fine structure and function of two macrophage-specific enhancer elements of the chicken lysozyme gene (E-2.7 kb and E-0.2 kb). Both increase their activities upon LPS induction, both contain multiple binding sites for similar or identical nuclear factors and both can be divided into two functional modules. For the E-0.2 kb enhancer we found a synergistic activity of the modules to be dependent on their distance. Binding sites for nuclear proteins within enhancer E-0.2 kb overlap substantially with the previously identified progesterone/glucocorticoid receptor binding site, which is required for steroid induction of lysozyme transcription in the oviduct.

Animals↗
PubMed1987

Lysozyme gene activity in chicken macrophages is controlled by positive and negative regulatory elements.

The chicken lysozyme gene is constitutively active in macrophages and under the control of steroid hormones in the oviduct. To investigate which DNA elements are involved in the control of its expression in macrophages we performed transient DNA transfer experiments with two different types of plasmids: 5'-deletion mutants of the upstream region of the chicken lysozyme gene and different fragments from this area in front of the thymidine kinase promoter (herpes simplex virus), each placed in front of the CAT (chloramphenicol acetyl transferase) coding sequence. Two enhancers (E-2.7 kb and E-0.2 kb) were characterized. They are active in macrophages, but not in chicken fibroblasts. Furthermore a negative element (N-2.4 kb) was identified, which is active in fibroblasts and promyelocytes, but not in mature macrophages. The combined action of all three elements contributes to the observed lysozyme gene activities: no activity in fibroblasts, moderate activity in promyelocytes and high activity in mature macrophages.

Animals↗
PubMed1987

Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements.

The chicken lysozyme gene is constitutively expressed in macrophages. Transfection of recombinant genes containing different portions of the lysozyme 5' upstream region revealed the existence of two negative transcriptional elements within 1 kb upstream of the start sites. Both elements placed upstream or downstream of a heterologous promoter-gene unit repress transcription independent of their orientation and are therefore called silencer elements, although their repressing activities 3' of the gene are reduced. One silencer (N-1.0 kb) at position -1 kb consists of the central region of the chicken middle repetitive sequence element CR1 and can be divided into two functional domains. N-1.0 kb is active in all cell types tested. The other silencer (N-0.25 kb) at position -0.25 kb shows reduced activity in primary macrophages. Despite their different specificities, the activity of both silencer elements can be influenced similarly. An inverse linear relationship between the transcriptional activity of the tested constructs and the potential inhibition by the silencer elements was found: weak transcription units can be strongly repressed, whereas strong transcription units can be only weakly repressed. Such a mechanism may help to turn off completely a particular gene in situations or tissues where strong positive regulators are inactive.

Animals↗
PubMed1987

Estimates of the population pharmacokinetic parameters and performance of Bayesian feedback: a sensitivity analysis.

We investigated the influence of bias in the estimates of the population pharmacokinetic parameters on the performance of Bayesian feedback in achieving a desired drug serum concentration. Three specific cases were considered (i) steady-state case, (ii) lidocaine example, and (iii) mexiletine example. Whereas in the first case both the feedback and the desired concentration represented steady-state values, in the lidocaine and mexiletine examples the feedback concentration was assumed to be sampled shortly after starting therapy. RMSE was used as a measure of predictive performance. For the simple steady-state case the relationship between RMSE and bias in the parameter estimates describing the prior distribution could be derived analytically. Monte Carlo simulations were used to explore the two non-steady-state situations. In general, the performance of Bayesian feedback to predict serum concentrations was relatively insensitive to bad population parameter estimates. However, large changes in RMSE could be observed with small changes in the true variance component parameters in particular in the intraindividual residual variance, sigma 2 epsilon, indicating that the prediction interval, in contrast to point prediction, is sensitive to bias in the estimates of the population parameters.

Bayes Theorem↗
PubMed1987

[Determination of formaldehyde concentration in a low-pressure sterilizer].

Two methods are described in determining the concentration of Formaldehyde in the sterilisation chamber of a regular commercial sterilizer. The measurement and flow of the concentration is ascertained during a routine sterilization procedure. With regard to the biological efficiency test of the examined apparatus the stability of the active Formaldehyde concentration is controlled. The difficulty in the determination of the Formaldehyde in such sterilizers is due to the fact that samples must be taken at a reduced pressure of 200 mbar. We have developed two different sampling methods. By employing the first continual collection method Formaldehyde gas is drawn out of the sterilization chamber with a high vacuum pump and conveyed with hydrogen into a nickel catalysator, whereby Methane is formed. The determination of Methane is carried out with a flame ionisation detector (F.I.D.). The results of the F.I.D. method are between 10.1-10.8 mg Formaldehyde per litre of gas. It is possible to detect a slight, even reduction in the Formaldehyde concentration throughout a period of 90 min. With the second discontinual method of determination vacuum tubes are employed which are furnished with external magnetic valves for control. By opening the magnetic valves briefly during the pre-vacuum therewith causing loss of pressure, Formaldehyde gas can be collected in the vacuum tubes throughout the sterilization procedure. The determination of the samples extracted by the discontinual method is carried out spectrophotometrically using the p-Rosanilin method after Miksch et al. The second method of determination shows values of 9.0-9.8 mg/l (Sx = 0.8 mg/l). These results lie somewhat lower than those of the F.I.D. determination. The flow of the concentration during 90 min. shows an average reduction of 7.4% and matches exactly the curve which was obtained by the F.I.D. method. By measuring the Formaldehyde concentrations which goods are subjected to in normal sterilization procedure it is possible to examine the efficacy of Formaldehyde sterilizers under regular conditions. Only by quotation of the Formaldehyde concentration present is it possible to reproduce details on sterilization times of treated articles.

Calibration↗
PubMed1986

Somatostatin inhibits fusion of pituitary secretion vesicles with the plasma membranes.

Somatostatin has been found to inhibit secretion vesicle fusion with the iodinated (125-I) inside-out plasma membrane vesicles (both were isolated from the anterior pituitaries). This effect of somatostatin was specific and dose-dependent (half-maximal effect at 10(-9) M). Calmodulin (10 microM), but not cyclic AMP, enhanced the fusion process between the two organelles and somatostatin inhibited calmodulin-stimulated fusion. These observations suggest that one facet of somatostatin action on hormone secretion may be its inhibition of secretion vesicle fusion with the plasma membrane.

Animals↗
PubMed1986

Somatostatin receptors are biologically active before they are inserted into the plasma membrane.

We have examined the biological activity of intracellular somatostatin (SRIF) receptors in cultured rat anterior pituitary cells. We used digitonin-permeabilized cells to introduce free SRIF intracellularly and chloroquine-treated cells to promote intracellular accumulation of SRIF via a receptor-mediated pathway. At a concentration of 0.001%, digitonin (3-min incubation at 37 C) allowed [125I]SRIF to enter the cells without affecting cell viability. Autoradiography of [125I]SRIF demonstrated its association with secretion vesicles (28%), nuclei (25%), and other intracellular organelles. An acid wash technique that removes cell surface-bound ligand revealed that both digitonin-permeabilized cells and chloroquine-treated cells accumulated approximately twice as much intracellular SRIF as did control cells. The biological activities of intracellular SRIF accumulated via two different pathways, receptor mediated and through digitonin-produced pores in the plasma membrane, were different. In chloroquine-treated cells, the accumulation of intracellular SRIF did not result in its additional biological effect. SRIF inhibited GH-releasing factor-induced GH release from 578 +/- 12 to 168 +/- 9 ng/10(6) cells X 30 min, which did not differ from the control value. Cells incubated with digitonin demonstrated normal basal (160 +/- 9 ng/10(6) cells X 30 min) and GH-releasing factor-stimulated GH release (564 +/- 11 ng/10(6) cells X 30 min). However, the inhibitory action of SRIF in these cells was approximately 30% greater (98 +/- 8 ng/10(6) cells X 30 min) than that in either control or chloroquine-treated cells, suggesting that SRIF freely admitted intracellularly produces additional biological activity. These observations confirm the presence of the intracellular receptors and suggest that these receptors exist in a biologically active form.

Animals↗