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Biomedical subjects

A Bauer

Publications and source records attributed to A Bauer.

At least 19 recordsLinked to original sources

Muscarinic desensitization after septal lesions in rat hippocampus: evidence for the involvement of G-proteins.

Three days after bilateral septal lesions, regional and laminar densities of the muscarinic acetylcholine receptors of the dorsal rat hippocampus were studied. The concentration of [3H]N-methylscopolamine binding sites and muscarinic M1 and M2 receptor subtypes, as well as the affinity of muscarinic receptors and their sensitivity to modulation by 5-guanylylimidodiphosphate were analysed by quantitative receptor autoradiography. The measurement of these parameters was performed with a computerized image-processing system allowing a spatial resolution down to the level of single hippocampal layers. No postlesional changes of the density of M1 receptors were detected. M2 receptors showed a remarkable decrease in concentration (less than 21%) in some hippocampal layers after septal lesions. In competition experiments the affinity of muscarinic receptors for the cholinergic agonist carbamylcholine chloride decreased significantly in all hippocampal subregions and layers of the lesioned animals. In contrast to controls, the sensitivity of muscarinic receptors of the lesioned animals could not be modulated by 5-guanylylimidodiphosphate. These findings demonstrate a desensitization of muscarinic receptors in the rat hippocampus three days after septal lesions, which is caused by changes of the coupling of guanine nucleotide-binding proteins to muscarinic receptors. Therefore, the lesion-induced alteration of the muscarinic receptor-effector complex is a major aspect of the hippocampal plasticity after cholinergic denervation.

Animals

Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results.

Outpatients (n = 15) with metastasizing far advanced colorectal cancers received immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28 days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m. once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin i.m. All patients had had previous surgery and/or chemotherapy and had progressive disease upon entering the study. Two months after onset of therapy a partial tumor regression was documented in one and a stable disease in 6 other patients by abdominal ultrasonography, decrease of the tumor markers carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography, which may also be attributed to the natural course of disease. Mean survival time was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well tolerated by all patients without side effects.

Adjuvants, Immunologic

Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms.

The T-cell antigen receptor (TCR) consists of an antigen-binding heterodimer, termed Ti, which is noncovalently associated with the invariant CD3 subunits (gamma, delta, epsilon, zeta, and eta). The CD3 zeta and -eta subunits form either homodimeric or heterodimeric structures in turn associated with the other components of the TCR complex. This feature increases the structural complexity of TCRs by creating "isoforms." Both CD3 zeta and -eta are thought to play an important role in signal transduction triggered by antigen/major histocompatibility complex. To compare signaling functions of TCR isoforms, MA5.8, a CD3 zeta-eta- variant of the cytochrome c-specific, I-Ek-restricted T-cell hybridoma 2B4.11, was stably transfected with cDNAs encoding CD3 zeta and/or CD3 eta, and resulting clones were characterized. The findings indicate that signals inducing Ca2+ mobilization, phosphatidylinositol turnover, and interleukin 2 production are each transmitted by the above TCR isoforms. In contrast, tyrosine phosphorylation of the CD3 zeta subunit but not the CD3 eta subunit follows TCR stimulation. Given the general importance of tyrosine phosphorylation for receptor signaling, it is likely that this difference between TCR isoforms plays a regulatory role in T-lineage function by qualitatively or quantitatively altering signaling events.

Animals

Low-dose subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis.

We evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty-five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 +/- 5.4% to 28.1 +/- 6.7% (P less than 0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 +/- 1.8% to 25.2 +/- 2.4% (P less than 0.01) within the first 2 weeks and up to 27.5 +/- 3.7% (P less than 0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side effects.

Adult

Regional and laminar distributions of alpha 1-adrenoceptors and their subtypes in human and rat hippocampus.

The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists

[Determination of antithyroid antibodies by an immunoenzymatic method; an adaptation for expressing results in international units].

Solid phase immunoenzymatic methods (ELISA) have been developed for the determination of antithyroglbulin (ATG), antimicrosomal (AMc) and antimembrane (ATMA) antibodies in blood serum. The results have been expressed in international units (IU). The level of nonspecific reaction was determined on the basis of 30 samples of blood serum obtained from healthy donors. The double standard deviation values amounted to 8 IU for antithyroglobulin antibodies, 17 IU for antimicrosomal antibodies and 53 IU for antimembrane antibodies at the serum dilution of 1:100. The values of double standard deviation obtained for the healthy donors correspond to the borderline between the positive serum samples and those containing no autoantibodies. The level of autoantibodies in patients with autoimmune diseases of the thyroid varied considerably ranging from complete absence to several thousand units per milliliter in single cases. Antithyroglobulin antibodies were determined simultaneously by using the described method and the commercial kit (Walker, Cambridge) and the results obtained by the two methods were compared. A linear correlation with the correlation coefficient r = 0.93, p < 0.001 was obtained. A good but nonlinear correlation was demonstrated with the methods expressing the results in titre values.

Autoantibodies

["Adopt a healthy lifestyle..". A motivation program to control risk factors of arteriosclerosis in students].

To reduce coronary heart disease risk factors in children an intervention study among 9-year old students and their 40-year old parents was implemented. 348 subjects were in grade 3 at six elementary schools. All students and some 50% of their parents participated in a comprehensive health instruction and nutrition education program. In addition, an integrated school-based clinic offered facilities to take part in a cholesterol screening activity attracting 89% of students and 50% of parents. As a result, 19% of the students and 51% of the parents whose cholesterol levels exceeded the WHO recommendation of 200 mg/dl were counselled for that reason. Besides that, natural opportunities to lose weight and to reduce fat consumption were trained in an integrated approach. Health knowledge was tested and proved to have increased by 50% at the end of the activities. The programme may reduce chronic disease risk by increased efforts to improve repetition and implementation of health activities.

Arteriosclerosis

Characterization of thymus-derived lymphocytes expressing Ti alpha-beta CD3 gamma delta epsilon zeta-zeta, Ti alpha-beta CD3 gamma delta epsilon eta-eta or Ti alpha-beta CD3 gamma delta epsilon zeta-zeta/zeta-eta antigen receptor isoforms: analysis by gene transfection.

To characterize the function of the CD3 eta subunit of the T cell receptor (TCR), we have used cDNAs encoding CD3 zeta, CD3 eta, or both to reconstitute a variant of a cytochrome c-specific, I-Ek-restricted murine T cell hybridoma, termed MA5.8, which lacks CD3 zeta and CD3 eta proteins. We provide direct evidence that assembly and surface expression of TCRs can be mediated by either of these subunits separately or together. However, the level of TCR expression on zeta transfectants is up to one order of magnitude greater than that on eta transfectants, implying that CD3 eta is weakly associated with the pentameric Ti alpha-beta CD3 gamma delta epsilon complex and/or inefficient at salvaging the incomplete TCR from lysosomal degradation. As a component of the TCR, the CD3 eta subunit preferentially forms a heterodimer with CD3 zeta, but is also able to form a CD3 eta-eta homodimer. Crosslinking of Ti alpha-beta CD3 gamma delta epsilon zeta-zeta, Ti alpha-beta CD3 gamma delta epsilon eta-eta, or Ti alpha-beta CD3 gamma delta epsilon zeta-zeta/zeta-eta TCR isotypes with anti-CD3 epsilon monoclonal antibody or a cytochrome c peptide epitope on I-Ek antigen-presenting cells mediates signal transduction resulting in reversible cell-cycle arrest of transfected clones. Given the potential for diversity of signals generated by these functional TCR isotypes and the expression of the CD3 eta gene product in the thymus, CD3 eta is likely to play a role in selection and/or activation of thymocytes during development.

Animals

Interferon gamma encapsulated into liposomes enhances the activity of monocytes and natural killer cells and has antiproliferative effects on tumor cells in vitro.

The effects of human interferon gamma (IFN gamma) encapsulated into liposomes were investigated in vitro. Monocytes were induced to release a cytotoxic factor with either IFN gamma encapsulated into liposomes, free IFN gamma or lipopolysaccharide (LPS). If IFN gamma was applied in the liposomal form, less IFN activity was required to stimulate monocytes. Most of the cytotoxic factor was secreted during the first 4 h of stimulation. The cytotoxic factor in supernatants from PMNLs was completely neutralized by a monospecific polyclonal antiserum to tumor necrosis factor (TNF). Combining subthreshold doses of IFN gamma liposomes or IFN gamma with lipopolysaccharide synergistically enhanced the release of TNF. In fluorescence analysis, altered expression of the class II HLA-DR antigen on LeuM3 positive monocytes was induced with IFN gamma liposomes as well as with IFN gamma. Not only monocytes but also natural killer (NK) cells were stimulated to higher cytotoxicity by IFN gamma liposomes in a dose-dependent manner. In comparison with IFN gamma, the same amount of activity was necessary for adequate stimulation of NK-cells against the K562 target cells. Furthermore, the antiproliferative effects of IFN gamma liposomes and free IFN gamma on several human tumor cell lines was compared. Among several cell lines tested, U937 and A549 turned out to be sensitive to IFN gamma, and both cell lines reacted with 50% growth inhibition at a lower amount of gamma presented by liposomes than in the free form. These data show production of IFN gamma liposomes which possess immunomodulatory and antiproliferative activity in vitro. In several of the test systems studied, liposome-encapsulated IFN gamma was more effective than free IFN gamma.

Cell Division

Growth of avian adeno-associated virus in chicken cells transfected with fowl adenovirus serotype 1 DNA.

Using the chloroquine-modified calcium phosphate coprecipitation technique, fowl adenovirus serotype 1 (FAV 1) DNA transfects efficiently chicken cell cultures. Infection of FAV 1 DNA transfected cells with helper dependent avian adeno-associated virus (AAAV) results in the production of AAAV progeny, being detected by an indirect immunofluorescence assay. These findings indicate that FAV 1 DNA introduced into the host cell promotes actively the growth of AAAV.

Adenoviridae Infections

Ferromagnetic isolation of endosomes: a novel method for subcellular fractionation of Xenopus oocytes.

A novel method has been developed using ferric particles to label endosomes, and to achieve magnetic sorting of the various endocytic compartments involved in lipoprotein uptake into cells. Ferric particles conjugated to a receptor-recognized ligand are bound to coated membrane pits and become internalized into the cytoplasm inside coated vesicles. After apparent fusion of the vesicles to tubular endosomes, the conjugates accumulate and finally discharge into multivesicular endosomes. Pulse-chase experiments elucidate the pathway of internalized conjugates and allow both early compartments (pinosomes and tubular endosomes) and late compartments (multivesicular endosomes and storage organelles) to be selectively labelled. After ferroloading of the various transport compartments, the cells are homogenized and subcellularly fractionated. Sorting of labelled endosomes is performed by a specially designed "free-flow" magnetic chamber. Prophase I-arrested oocytes of the toad Xenopus laevis are used as a model system for studying the transport pathway and the conversion of the yolk precursor vitellogenin. It is possible to follow the route of internalization of vitellogenin-iron conjugates via coated pits, coated vesicles, uncoated vesicles, tubular endosomes, multivesicular endosomes, and light primordial yolk platelets. These endosomes shuttle the ferric particles together with the vitellogenin from oolemma to performed heavy yolk organelles which are still growing. In addition, these various compartments can be isolated according to their function and subjected to electron microscopy and to gel electrophoresis for detailed characterization of their limiting membranes as well as their contents.

Animals

Pharmacokinetic study of liposome-encapsulated human interferon-gamma after intravenous and intramuscular injection in mice.

We encapsulated human interferon-gamma (HuIFN-gamma) into liposomes and analyzed whether this preparation prevented the rapid decay of IFN-gamma in the serum of C57BL/6 mice after intravenous or intramuscular injection. Furthermore, we compared the serum decay curve of liposomal and free IFN-gamma. Whereas the intramuscular injection of IFN-gamma resulted in a serum curve with entrance compartment and subsequent biphasic elimination, intravenously injected IFN-gamma was distributed and eliminated in a biphasical manner from serum. Extremely prolonged serum titers are caused by IFN-gamma liposomes with a phospholipid composition of dimyristoylphosphatidylcholine/cholesterol/dicetylphosphate and an average particle size of 333 nm. Intramuscular injection of 2.5 mumoles liposome suspension with an antiviral activity of 4.3 x 10(3) IU/mouse resulted in longer-lasting serum titers than intravenously injected liposomes of a different charge with 2.5 mumoles and 1.2 x 10(5) IU/mouse. Liposomes after intravenous injection could be detected for up to 62 h at a titer of 20 IU/ml serum. Intramuscularly injected liposomes of the lower activity still had a titer of 30-80 IU/ml after 80 h p.i.

Animals

Ferromagnetic isolation of endosomes involved in vitellogenin transfer into Xenopus oocytes.

The transport pathway of the yolk precursor vitellogenin (VTG) has been followed using the techniques of ferrolabeling and ferromagnetic sorting, coupled with electron microscopic visualization. Vitellogenin conjugated to colloidal ferric particles of ca. 11 nm is selectively transported from the oolemma to the yolk platelets of vitellogenic Xenopus oocytes after gonadotropin stimulation of the female. Several cortical membrane compartments, labeled or unlabeled with ferric particles, are involved in the internalization and the transfer of vitellogenin to the yolk platelets. 1) Coated pits apparently fuse with coated vesicles, and coated vesicles fuse with each other in the outermost cortical cytoplasm. 2) Vesicles, depleted of their clathrin coat, fuse with cortical tubular endosomes and discharge their contents into yolk endosomes. 3) These endosomes are the direct precursors of the yolk organelles. 4) Endocytic vesicles fuse only with primordial yolk platelets of type I and not with type II or fully grown yolk platelets. After pulse-chase loading with ferric particles conjugated to vitellogenin and subsequent subcellular fractionation of the oocytes, ferromagnetic sorting of the various vesicle populations has been performed by using a "free-flow magnetic chamber". This novel method enables specification and characterization of purified endosomal compartments that accumulate protein yolk in Xenopus oocytes.

Animals

[Aortic aneurysm and aortic injury--surgical treatment and follow-up].

This study summarizes our experience with 90 patients (68 male and 22 female, mean age 57.2 years). From Jan. 1980 to Feb. 1990, 51.1% underwent surgery for dissection of the aorta; the rest for acute aortic ruptures, false and true aneurysms. Procedures with reconstruction of the aortic arch were performed in cases of deep hypothermia and circulatory arrest (no fatal courses). The overall death rate was 18.8% (emergency 29.5%, elective 8.7%). Acute dissections Type I had the highest perioperative mortality with 29.4%. The leading causes of early death were myocardial infarction (23.5%) and cerebral injury (23.5%). Therefore coronary angiograms should be performed preoperatively in older patients. A major problem in our experience is the long-term followup examination which should remain the surgeon's responsibility.

Adolescent

The effect of diagnosis and educational level on therapists' treatment decisions in a regional psychiatric outpatient clinic.

The aim of this study was to investigate a random sample of psychiatric patients referred for treatment at a psychiatric out-patient unit with the purpose of evaluating their demographic structure, epidemiological data, therapist's decision-making process and the interaction between these factors. Positive correlations were found between diagnosis and variables connected to therapeutic decisions. Variables associated with therapeutic decision were found to be influenced by diagnosis at intake as well as by educational status of the patient. Other findings and possible explanations for correlations observed are presented.

Adult

Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

Adjuvants, Immunologic

[Institutional establishment of pathologic anatomy in the 19th century at universities in Germany, German-speaking Switzerland and Austria].

The institutionalization of an academic discipline in the university system is a complex process influenced by several intra- and extrascientific, personal and economic factors. Starting with pathological anatomy at the beginning of the 19th century, we analysed its development from a subsidiary to a fully established discipline. We ascertained different stages of institutionalization:lectureship, associate chair, chair, institute. At each stage we found supporting as well as hindering factors. It could be shown that the structure of the German academic system was especially conductive to the establishment of the new discipline.

Austria