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R Bauer

Publications and source records attributed to R Bauer.

At least 289 records · Page 16Linked to original sources
PubMed1993

Suppression of graft-versus-host disease by succinyl acetone in a rat allogeneic bone marrow transplantation model.

The efficacy of succinyl acetone (SA, 4,6-dioxoheptanoic acid) was explored in the allogeneic rat bone marrow transplant model of graft-vs.-host disease. Lethally irradiated Wistar Furth rats receiving Fischer 344 allogeneic bone marrow and spleen cells developed severe GVHD, resulting in mortality at 25-45 days posttransplant. Treatment for 14 days with 250 mg/kg/day of SA by Alzet osmotic pumps implanted subcutaneously 3 days before cell transfer prevented GVHD and produced long-term survivors that were allogeneic hematopoietic chimeras. SA doses below 250 mg/kg/day and treatment for less than 14 days were less efficacious. Initiation of SA therapy could be effectively delayed up to 7 days after BMT. Pharmacokinetic studies with i.v. bolus administration in normal CD rats revealed a plasma mean residence time that increased with dose and a systemic clearance that decreased with dose. Three dose-dependent half lives were apparent (ca. 7-18 min, 0.8-3 hr, and 12 hr). The s.c. bioavailability was ca. 82%. Relatively constant plasma SA levels were obtained with s.c. Alzet osmotic pumps, indicating no change in clearance with continuous exposure. Allogeneic BMT exerted no major influence upon SA clearance. These studies show that SA is a robust therapeutic agent that suppressed GVHD in the allogeneic rat BMT model under a variety of circumstances.

Animals↗
PubMed1993

An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2.

AP-2 is a retinoic acid-inducible and developmentally regulated activator of transcription. We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A). This protein contains the activation domain of AP-2 and part of the DNA binding domain but lacks the dimerization domain which is necessary for DNA binding. Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. Both transient and stable transfection experiments show that AP-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid. Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes. To determine the mechanism by which AP-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an AP-2 consensus site, it strongly inhibits binding of the endogenous AP-2 present in PA-1 cell nuclear extracts. However, DNA sequence-specific binding of bacterially expressed AP-2A cannot be inhibited by bacterially expressed AP-2B. Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts.

Alternative Splicing↗
PubMed1993

Familial cosegregation of affective disorder and Hailey-Hailey disease.

We report on a family with co-occurrence of affective disorder and Hailey-Hailey disease in two brothers and the mother. The putative chromosomal locus of Hailey-Hailey disease, which is a rare dominantly inherited dermatosis, may be a promising candidate region for genetic studies in affective disorder.

Bipolar Disorder↗
PubMed1993

Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis.

Preliminary reports suggest that PTH is secreted in a pulsatile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age-matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study.

Adult↗
PubMed1993

Mechanism of action of methotrexate: experimental evidence that methotrexate blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target cells.

Interleukin 1, a multifunctional cytokine, plays a central role in inflammatory processes and induction of the immune response. Target cells possess 200-5000 (or more) interleukin 1 receptors per cell, but they exhibit a full biological response when only 1-2% of these receptors are occupied by interleukin 1 alpha or 1 beta. Methotrexate has been reported to be beneficial in several inflammatory and autoimmune diseases. On the other hand, many of these diseases are known to share an overproduction of interleukin 1. It has been demonstrated that methotrexate has no influence on the interleukin 1 synthesis, so we focused our attention on the ability of methotrexate to interfere with the binding of interleukin 1 beta to the interleukin 1 receptor. The experiments were performed on monocytes, lymphocytes and granulocytes using a recombinant human cytokine probe. Methotrexate led to an astonishing decrease in the binding of interleukin 1 beta to the interleukin 1 receptor of peripheral blood cells, whereas methylprednisolone and indomethacin were not inhibitory. The inhibitory effect of methotrexate was dose dependent. An excess of interleukin 1 beta abolished the inhibition of cytokine binding by methotrexate. We also demonstrated that methotrexate does not affect the integrity of the interleukin 1 receptor or of the target cells. Our results demonstrate that methotrexate blocks the interleukin 1 beta-interleukin 1 receptor pathway. Methotrexate is therefore another interleukin 1 inhibitor and a clinically efficient anticytokine.

Flow Cytometry↗
PubMed1993

[AP-2: a nuclear effector of malignant transformation by ras oncogene].

We have applied a series of cell clones established from the human teratocarcinoma cell line PA-1 to study the effect of malignant transformation by ras-oncogenes on the regulation of cell growth and differentiation. A particular aim of this study was to identify nuclear gene-regulatory factors that are affected by ras-transformation. We show that a key nuclear target of ras is the transcription factor AP-2. AP-2 function is inhibited through the ras-controlled signal transduction cascade by at least two different mechanisms, i.e. inhibition of an AP-2 coregulatory factor and by expression of an alternatively spliced inhibitory AP-2 protein.

Alternative Splicing↗
PubMed1993

Relationship of antibodies against CD4+ T cells in HIV-infected patients to markers of activation and progression: autoantibodies are closely associated with CD4 cell depletion.

Antibodies against lymphocytes have been shown in human immunodeficiency virus (HIV)-infected patients, but their relevance in the pathogenesis of acquired immune deficiency syndrome (AIDS) remains controversial. We investigated increased levels of lymphocyte surface Ig and antibodies against CD4+ T cells in the plasma. The relationship to CD4 cell depletion and serological parameters were analysed. A three-colour flow cytometric method was used to detect surface Ig on the surface of patients' cells and antibodies in the plasma of the patients. We observed a high percentage of patients with increased surface Ig on CD4+ T cells (94%-47/50). Antibodies in the plasma reacting with healthy donors' CD4+ T cells were detectable in 72% (23/32) of the patients. CD4 cell-surface Ig correlated well with surface Ig on different T-cell subpopulations but not with increased surface Ig on B cells. Only one control showed elevated surface Ig, plasma antibodies against lymphocytes were not detectable. Surface Ig levels of CD4+ T cells were closely associated with the CD4 cell number in HIV-infected patients of all stages of disease (r = -0.67, P = 0.00005). Other lymphocyte subsets' surface Ig did not show a significant association to CD4 cell depletion. Surface Ig and antibodies against CD4+ T cells were not related to levels of beta 2-microglobulin, p24 antibodies or interleukin-6 (IL-6), and did not depend on hypergammaglobulinaemia. In conclusion surface Ig on CD4+ T cells is likely to have an autoantibody origin. The high prevalence and association to CD4 depletion support the view that autoimmune phenomena could be involved in the pathogenesis of AIDS.

Autoantibodies↗
PubMed1993

Left ventricular function assessed with echocardiography and myocardial perfusion assessed with scintigraphy under dipyridamole stress in pediatric patients after repair for anomalous origin of the left coronary artery from the pulmonary artery.

Twenty-three patients who underwent operation for anomalous origin of the left coronary artery from the pulmonary artery were reexamined with two-dimensional echocardiography and thallium 201 perfusion imaging. Follow-up studies were performed 0.6 to 16.2 years (median 2.9 years) after operation. In 22 of 23 patients, a two coronary artery system had been established by implantation of the left coronary artery into the aorta (n = 8) or by anastomosis of the left subclavian artery with the left coronary artery (n = 14). The left coronary artery had been ligated in only one patient. For stress testing, 0.8 mg dipyridamole per kilogram body weight was infused in a 10-minute period in 20 of the 23 patients. High-dose dipyridamole infusion increased mean heart rate (98.1 +/- 27.1 to 122.3 +/- 19.2 beats/min, p < 0.001) and mean left ventricular ejection fraction (54.8% +/- 11.8% to 61.3% +/- 12.5%, p < 0.05) and decreased left ventricular end-diastolic volume index (38.8 +/- 26.7 to 29.9 +/- 8.3 ml/m2, p < 0.005). At rest, left ventricular dimensions were abnormal in only one patient, in whom the anastomosis with the left coronary artery proved to be occluded, as seen with subsequent angiography. Left ventricular function seen with two-dimensional echocardiography was normal in 19 patients and was compromised in 3 (all of whom had major structural anomalies of the left ventricle, such as left ventricular aneurysm, occlusion of the anastomosis, or mitral valve prosthesis). Patients with R-wave loss as seen with preoperative electrocardiography tended to have larger left ventricular volumes at follow-up (69.2 +/- 56.5 ml/m2 versus 32.4 +/- 9.6 ml/m2, p < 0.07). Ten of 20 patients had normal thallium 201-perfusion scans. In 9 of 20 patients defects revealed by permanent thallium 201-perfusion were observed and determined to be myocardial scars. Transient perfusion defects under dipyridamole stress with redistribution at rest occurred in three children, two of whom also had permanent thallium 201 defects. None of the three patients had angina-like symptoms or S-T segment changes during dipyridamole stress. Left ventricular ejection fraction, however, decreased severely during dipyridamole infusion in the single patient with ligature of the left coronary artery. The two remaining patients had normal echocardiographic left ventricular function under stress, and the diagnosis of myocardial ischemia as seen with scintigraphy must be questioned.(ABSTRACT TRUNCATED AT 400 WORDS)

Child, Preschool↗
PubMed1992

The mapping by high-pH anion-exchange chromatography with pulsed amperometric detection and capillary electrophoresis of the carbohydrate moieties of human plasma alpha 1-acid glycoprotein.

The reducing oligosaccharides released from alpha 1-acid glycoprotein (AGP) by conventional hydrazinolysis have been analyzed by two different mapping techniques, using high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) and capillary electrophoresis (CE) with uv detection at 190 nm. The CE measurements proved about 4000 times more sensitive than the measurements by HPAE-PAD. The N-glycan pool was fractionated by Mono Q anion-exchange chromatography, and individual fractions so obtained were desialylated using Vibrio cholerae neuraminidase. The resulting asialo-N-glycans were further analyzed by HPAE-PAD, revealing 2 major, 4 intermediate, and 4 small peaks and at least 3 spikes, which counted for at least 13 different asialo-N-glycans. The carbohydrate structures were tentatively assigned by comparison of the Mono Q-separated N-glycans with the known AGP carbohydrate structures and known structures contained in a mapping database that allows structural assignment of N-glycans by mere comparison of retention times. In addition to the hitherto known AGP carbohydrate structures, we have tentatively identified a number of sulfated N-glycans that are currently being analyzed in more detail. We have also compared the glycan pools recovered from AGP using hydrazinolysis and glycopeptidase F (PNGase F). Approximately 40 distinct peaks could be detected in the hydrazinolysis-derived N-glycan pool by either technique (HPAE-PAD and CE), while about 30 distinct peaks were detected in the N-glycan pool derived by PNGase F digestion of the tryptic AGP digest of the same batch of AGP. These differences were attributed to an increased desialylation (approximately 3 mol%) during hydrazinolysis, based on the detection by HPAE-PAD and CE of free sialic acid and monosialylated oligosaccharides in the glycan pool derived by conventional hydrazinolysis. The integrity of the N-glycans' chitobiose core was examined by 500-MHz 1H NMR spectoscopy. The hydrazinolysis procedure could be optimized such that the hydrazinolysis-derived N-glycan pool was chromatographically essentially identical to the PNGase F-derived N-glycan pool. Hydrazinolysis proved best, with practically no loss of N-acetlylneuraminic acid and the closest resemblance to the PNGase F-derived N-glycan pool, using an automated apparatus. Notably, it was recognized that, in our hands, PNGase F digestion in the presence of sodium dodecyl sulfate resulted in partial desialylation of the liberated N-glycans.

Capillary Action↗
PubMed1992

Monofunctional DNA-platinum(II) adducts block frequently DNA polymerases.

The question of whether monofunctional DNA platinum(II) adducts block synthesis of DNA by purified DNA polymerases of different types and origin has been investigated by comparing the time dependence of synthesis arrest and of DNA adduct formation. Activated salmon testis DNA is used as a suitable substrate for DNA synthesis allowing to probe inhibition by platinum(II) monoadducts for the variety of inherent template-primers. Reaction amplitudes are related to defined mixtures of dichloro and chloroaqua platinum(II) complexes. It is found that (i) all investigated DNA polymerases seem arrested (100% efficiency) at bifunctional DNA adducts. (ii) human DNA polymerase beta bypasses most of the monofunctional lesions of the three platinum(II) complexes investigated. (iii) Klenow fragment is blocked by monoadducts with increasing efficiency in the order cis-diamminechloroaquaplatinum(II) (0%) less than meso-[1,2-bis(2,6- dichloro-4-hydroxyphenyl)ethylenediamine] chloroaquaplatinum(II) (50%) less than trans-diamminechloro-aquaplatinum(II) (75%). (iv) Escherichia coli DNA polymerase I, Thermus aquaticus DNA polymerase, Physarum polycephalum DNA polymerase alpha, and calf thymus DNA polymerase alpha appear to be arrested by monoadducts. According to these examples, blocking efficiencies depend on the cis/trans-stereogeometry of fixation of the carrier ligands at platinum(II) residues, on the size/chemical nature of the platin(II) carrier ligand and on the type/origin of DNA polymerase.

Animals↗
PubMed1992

Comparison of magnetic resonance imaging with cross-sectional echocardiography in the assessment of left ventricular mass in children without heart disease and in aortic isthmic coarctation.

Although left ventricular (LV) mass may be important to judge effects of left-sided cardiac obstruction or hypertension, reproducible noninvasively determined normal data in the pediatric age group are scarce. To validate cross-sectional echocardiographic LV mass determination, our data were compared with LV mass assessed by magnetic resonance imaging (MRI). MRI was considered to be a good reference method because there is usually no problem in defining endo- and epicardial borders with MRI. LV mass was assessed in 14 children aged 5.3 years (10 days to 14.7 years) with a mean body surface area of 0.78 m2 (range 0.25 to 1.61). With cross-sectional echocardiography the epicardial and endocardial volumes were calculated using a Simpsons rule algorithm in the apical 2- and 4-chamber view. The difference between epi- and endocardial volumes was multiplied by 1.05 to yield the mass. Mass was assessed with MRI using a multislice technique; the area of each myocardial slice was calculated and multiplied with the slice thickness, and the resultant slice volumes were added to obtain the myocardial volume. On cross-sectional echocardiography, the mass was 55 g (range 12 to 126) or 64 g/m2 (range 46 to 79); on MRI it was 60 g (range 33 to 87) or 69 g/m2 (range 46 to 89). Regression analysis yielded an r value of 0.98 with a standard error of the estimate of 5.7 g or a 10% difference. In older children, LV mass determined by MRI was bigger than the one derived by echocardiography. It is concluded that cross-sectional echocardiography can reliably assess LV myocardial mass in pediatric patients.

Adolescent↗
PubMed1992

Contrast variation studies of clathrin coated vesicles by small-angle neutron scattering.

Structural information on clathrin coated vesicles has been obtained by small angle neutron scattering using contrast variation. A characteristic peak in the neutron scattering profile, which is apparent in 75% D2O, as well as in H2O, disappears when contrast matching the protein component of the coated vesicles in 42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases when matching out the protein coat of the clathrin coated vesicles. From the match point for the clathrin coated vesicles it is demonstrated that the clathrin cages do contain internal membrane. The mass of 34 MD and composition of 75% protein and 25% lipid found from the analysis of the small-angle scattering data are both in good agreement with the values reported in the literature. Electron microscopy gives an average outer diameter of 880 A for the coated vesicles and an average diameter of 460 A for the vesicle itself.

Biophysical Phenomena↗
PubMed1992

Cervical pheochromocytoma: a rare localization and a difficult diagnosis.

A 45-year-old hypertensive female with insulin-treated diabetes mellitus presented to our clinic with elevated urinary norepinephrine (NE) concentrations and a negative 131-metaiodobenzylguanidine (MIBG) scintigraphy, errouneously limited to the abdomen, for evaluation of a pheochromocytoma (Pheo). Despite antihypertensive medications blood pressure remained highly variable and frequently elevated. Further biochemical testing, including a glucagon provocation test and a clonidine-suppression test, revealed autonomous NE secretion. In order to avoid repeat MIBG-scintigraphy, other non invasive imaging techniques were performed, including real time sonography (7.5 MHz) of the neck which revealed a tumor. Fine needle aspiration of this tumor tissue demonstrated cells compatible with Pheo. Histology and immunohistochemistry of the excised tumor confirmed the diagnosis of Pheo. After surgical removal of the tumor, urinary and plasma NE levels normalized. Without any medication the blood pressure of the patient was now only slightly hypertensive. Only half of the daily insulin dose was needed to maintain the patient euglycemic.

Adrenal Gland Neoplasms↗
PubMed1992

Scoliosis correction by Cotrel-Dubousset instrumentation. The effect of derotation and three dimensional correction.

In 30 patients undergoing Cotrel-Dubousset instrumentation, computerized tomography was performed before and after surgery. The RAsag-angle was measured for each vertebral level. Coronal and sagittal translation were evaluated in the same computerized tomographic scans by means of a new method. Based on the hooks used, various sections of the spine were defined. In these sections relative rotation as well as relative sagittal and frontal translation were calculated by an algorithm comparing the most severely rotated or translated vertebra with the mean value of both end vertebrae. Significant correction of rotation did not occur in any of these sections. A significant increase of kyphosis, however, could be demonstrated in all thoracic sections. Above the second intermediate hook combined correction of all three parameters was achieved. Below this hook correction occurred almost independently in the frontal and sagittal planes.

Adolescent↗
PubMed1992

Reduced rate of uptake of zinc ions in a calf affected with the lethal syndrome A46 relative to clinically normal calves using whole body radio-isotope scanning of 62Zn.

Four clinically healthy control calves were scanned and blood clearance was determined from blood samples taken during the first hour after intravenous injection of 62Zn. Furthermore, one clinically healthy control calf and one calf suffering from the lethal hereditary syndrome A46 were scanned and blood samples taken from five min after intravenous and abomasal injection of 62Zn and onwards for a period of up to 26th. The results show a very fast liver uptake of 62Zn. The estimated rate of plasma/blood clearance and liver uptake for the control calves agrees with values derived from studies on other animals. In contrast, the A46 calf had a decreased rate of plasma/blood clearance and liver uptake relative to the control calves.

Animals↗