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Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 37 records · Page 2Linked to original sources

The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage.

The immunoglobulin diversity is restricted in fetal liver B cells. This study examined whether peripheral blood B cells of extremely preterm infants show similar restrictions (overrepresentation of some gene segments, short third complementarity-determining regions [CDR3]). DNA of rearranged immunoglobulin heavy chain genes was amplified by polymerase chain reaction, cloned, and sequenced. A total of 417 sequences were analyzed from 6 preterm infants (25-28 weeks of gestation), 6 term infants, and 6 adults. Gene segments from the entire V(H) and D(H) gene locus were rearranged in preterm infants, even though the D(H)7-27 segment was overrepresented (17% of rearrangements) compared to term infants (7%) and adults (2%). CDR3 was shorter in preterm infants (40 +/- 10 nucleotides) than in term infants (44 +/- 12) and adults (48 +/- 14) (P <.001) due to shorter N regions. Somatic mutations were exclusively found in term neonates and adults (mutational frequency 0.8% and 1.8%). We conclude that preterm infants have no limitations in gene segment usage, whereas the diversity of CDR3 is restricted throughout gestation.

Adult↗

Fungal brain abscesses in neonates: Sonographic appearances and corresponding histopathologic findings.

Extremely preterm neonates and neonates with predisposing conditions such as congenital or acquired immunodeficiency are at high risk for systemic fungal infection. Abscess formation in the brain is a severe complication that occurs in 70% of neonates with systemic fungal infection. Cerebral sonography can be used to diagnose abscesses in the brain in these patients. We report 2 sonographic presentations of fungal brain abscesses in neonates confirmed by postmortem histopathologic examination. The first patient, an extremely preterm neonate of 23 weeks' gestation with a systemic Candida albicans infection, had multiple small, round, hypoechoic lesions with echogenic rims in both brain hemispheres. The second patient, a term neonate with disseminated aspergillosis and DiGeorge syndrome, had a few large echogenic areas in the right periventricular region. Brain imaging should be considered in the diagnostic workup in neonates with suspected systemic fungal infection. Cerebral involvement can be diagnosed at the bedside with cerebral sonography.

Aspergillosis↗

Nitromusk compounds in women with gynecological and endocrine dysfunction.

Musk xylene (MX), musk ketone (MK), musk ambrette, musk moskene, and musk tibetene are synthetic fragrances. Between 1994 and 1996 these five nitromusk compounds (NMCs) were tested in the blood of 152 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. The testing was conducted by gas chromotography with mass-specific detector and mass spectrometry in a retrospective cross-sectional study. MX was detected in 95% and MK in 85% of the blood samples (>20 ng per liter whole blood). The median concentration of MX was 65.5 ng/L and the maximum level of MX was 1183 ng/L; the corresponding values for MK were respectively 55.5 and 518 ng/L. The other three NMCs were found in only a few patients or not at all. Significant associations between MX and MK concentrations were found in blood and different clinical parameters of the endocrine system. MX and MK may act centrally as a disrupter of the (supra-) hypothalamic-ovarian axis, which may result in a mild ovarian insufficiency. On the basis of our data, a reproductive toxicity and an endocrine effect of NMCs in women cannot be ruled out. Further experimental and clinical studies should be conducted.

Adult↗

[Neurotrophic ulcer as late sequela of trigeminal nerve excision].

A patient is presented with trophic ulcerations in the area innervated by the trigeminal nerve occurring 17 years after alcohol injection into the trigeminal ganglion and 16 years after excision of the trigeminal nerve. The mean period from time of trigeminal nerve injury to onset of the ulcer usually varies from several weeks to 1 or 2 years as reported in the literature. Our case demonstrates a late manifestation of the trigeminal trophic syndrome.

Aged↗

Arrangements of macro- and microchromosomes in chicken cells.

Arrangements of chromosome territories in nuclei of chicken fibroblasts and neurons were analysed employing multicolour chromosome painting, laser confocal scanning microscopy and three-dimensional (3D) reconstruction. The chicken karyotype consists of 9 pairs of macrochromosomes and 30 pairs of microchromosomes. Although the latter represent only 23% of the chicken genome they containalmost 50% of its genes. We show that territories of microchromosomes in fibroblasts and neurons were clustered within the centre of the nucleus, while territories of the macrochromosomes were preferentially located towards the nuclear periphery. In contrast to these highly consistent radial arrangements, the relative arrangements of macrochromosome territories with respect to each other (side-by-side arrangements) were variable. A stringent radial arrangement of macro- and microchromosomes was found in mitotic cells. Replication labelling studies revealed a pattern of DNA replication similar to mammalian cell nuclei: gene dense, early replicating chromatin mostly represented by microchromosomes, was located within the nuclear interior, surrounded by a rim of late replicating chromatin. These results support the evolutionary conservation of several features of higher-order chromatin organization between mammals and birds despite the differences in their karyotypes.

Animals↗

Effects of impulse noise stimulation on electrocorticogram and heart rate.

It is now recognized that high-level impulse noises penetrate the uterus of pregnant sheep, elevate thresholds of fetal auditory-evoked potential and produce damage to fetal inner ear hair cells. However, little is known about functional effects of airborne impulse noise on the late-term fetus. In the present study, the effects of a series of 20 impulses on the behavioral state of 6 fetal sheep were tested. Noise impulses produced 169.3 peak sound pressure level (pSPL) in air. Peak levels recorded near the fetal head averaged 161.1 dB. Impulses delivered to the fetus during periods of NREM sleep resulted in a decrease in average fetal heart rate (FHR) from 185 +/- 22 beats/min (bpm) before stimulation to 174 +/- 23 bpm 2-5 s after stimulation (p < 0.05). During REM sleep, an FHR acceleration occurred (before stimulation: 177 +/- 24 bpm, after stimulation: 189 +/- 31 bpm; p < 0.05). Impulse exposure during NREM sleep resulted in reductions in delta-, theta- and alpha-band powers. As a consequence, total power decreased from 100 to 72 +/- 16% (p < 0.05). During REM sleep, stimulation provoked a short decrease in total band power from 100 to 73 +/- 20% and a similar decrease in the theta- and beta-band powers. The results indicated that impulse noise evoked short-term alterations in FHR and cortical activity. These changes were mediated by auditory brain stem activation that led to cortical desynchronization during both NREM and REM sleep in late-term fetal sheep.

Acoustic Stimulation↗

In vitro validation and clinical testing of an indirect calorimetry system for ventilated preterm infants that is unaffected by endotracheal tube leaks and can be used during nasal continuous positive airway pressure.

Energy expenditure measurements in ventilated preterm infants are difficult because indirect calorimetry underestimates energy expenditure during gas leaks around uncuffed endotracheal tubes routinely used in preterm infants or during nasal continuous positive airway pressure (CPAP). We, therefore, developed a breath collector that simultaneously sampled expired air expelled at the ventilator outlet and escaping via the tube leak from the infant's mouth and nose. Our breath collector was combined with a proprietary calorimeter (Deltatrac II). In vitro validation was done by methanol burning (VO(2), 13.8 mL/min; VCO(2), 9.2 mL/min) during intermittent positive pressure ventilation (IPPV) with two commonly used ventilators (Sechrist IV-100B and Infant Star). Measurement error was determined at different ventilator flows, peak inspiratory pressures of 12-24 cm H(2)O, and during a complete tube leak. The mean measurement error with both ventilators was low (VO(2) +/- 3 %, VCO(2) +/- 2 %) even during a complete tube leak and did not increase with peak inspiratory pressure. The system response time was 2 min. In vivo measurements at the bedside were performed in 25 preterm infants (body weight, 537-1402 g). Energy expenditure during IPPV was 40 +/- 9 kcal/kg per day and 46 +/- 15 kcal/kg per day during nasal CPAP. The tube leak in the preterm infants studied during IPPV was 0 to 47 %, and during nasal CPAP 84 to 97 %. In conclusion, indirect calorimetry performed with our breath collector was accurate during IPPV and nasal CPAP and was unaffected by tube leaks.

Calorimetry↗

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

Adolescent↗

Expression and regulation of osteopontin and connective tissue growth factor transcripts in rat anterior pituitary.

Cell-cell interactions are important regulatory elements in anterior pituitary (AP) physiology. As model systems to study pituitary cell-cell interactions, AP cells kept either as monolayers or as organotypic reaggregate cultures were analyzed by differential display PCR. We identified six cDNA fragments (osteopontin (Opn), connective tissue growth factor (CTGF), alpha(v)-integrin, cathepsin H, lysozyme and O-acetyl GD(3) ganglioside synthase) that showed elevated expression in monolayers compared with reaggregate cultures and the AP. The adenohypophyseal mRNA expression of Opn and CTGF, two secreted signaling substances, was studied in more detail. In situ hybridization histochemistry revealed that Opn mRNA expression is restricted to a subpopulation of gonadotropes whereas CTGF hybridization signals could not be ascribed to any known cell type. Opn transcript levels were downregulated in the APs of lactating rats and decreased when rats received s.c. injections of 17beta-estradiol for 5 days. The mRNA expression was higher in male than in female rats and increased after gonadectomy. CTGF transcript levels were higher in male compared with female rats and were increased in pregnant rats and in rats treated for 5 days with triiodothyronine or dexamethasone. These results indicate that Opn and CTGF may be of physiological importance as local communication factors in the AP.

Animals↗

[Perioperative complications after heart valve replacement].

These days, the majority of perioperative complications resulting from operations on heart valves are more a consequence of the increasing age and morbidity of the patients and, despite all cardiac surgical and intensive care innovations, are still more the effect of the procedure on the other organ systems of the patient than being purely of a surgical nature. The surgical short- and long-term results after heart valve operations are significantly influenced by the early detection and adequate management of these manifold complications.

Adult↗

Human CLP36, a PDZ-domain and LIM-domain protein, binds to alpha-actinin-1 and associates with actin filaments and stress fibers in activated platelets and endothelial cells.

A 38-kd protein that associates with F-actin structures in activated platelets and endothelial cells was purified, cloned, and characterized. The protein contains an N-terminal PDZ motif, a large intervening sequence, and a C-terminal LIM domain and was identified as the human homolog of rat CLP36. The study showed that CLP36 associates with actin filaments and stress fibers that are formed during shape change and spreading of platelets and during migration and contraction of endothelial cells. CLP36 binds to alpha-actinin-1 as shown by coimmunoprecipitation, pull-down experiments, yeast 2-hybrid analysis, and blot overlay assays and colocalizes with alpha-actinin-1 along endothelial actin stress fibers. In contrast to alpha-actinin-1, CLP36 was absent from focal adhesions in both activated platelets and endothelial cells. The N-terminal part of CLP36 containing the PDZ domain and the intervening region, but not the LIM domain, targeted enhanced green fluorescent protein fusion proteins to stress fibers in endothelial cells. Yeast 2-hybrid analysis demonstrated that the intervening sequence, but not the PDZ or the LIM domain of CLP36, binds to the spectrinlike repeats 2 and 3 of alpha-actinin-1. The study further shows that CLP36 binds to alpha-actinin in resting platelets and translocates as a CLP36/alpha-actinin complex to the newly formed actin cytoskeleton in activated platelets. The results indicate that CLP36 binds via alpha-actinin-1 to actin filaments and stress fibers in activated human platelets and endothelial cells. The study suggests that CLP36 may direct alpha-actinin-1 to specific actin structures and at this position might modulate the function of alpha-actinin-1. (Blood. 2000;96:4236-4245)

Actin Cytoskeleton↗

Expression of thyrotropin-releasing hormone receptor 2 (TRH-R2) in the central nervous system of rats.

The distribution of the recently discovered thyrotropin-releasing hormone (TRH) receptor subtype TRH-R2 was studied in rat brain, pituitary, and spinal cord by in situ hybridization histochemistry and compared with the distribution patterns of the other elements of TRH signaling, namely TRH, TRH-R1, and the TRH-degrading ectoenzyme (TRH-DE). In contrast to the very restricted mRNA expression of TRH-R1 in the central nervous system, TRH-R2 mRNA was widely distributed with highest transcript levels throughout the thalamus, in the cerebral and cerebellar cortex, medial habenulae, medial geniculate nucleus, pontine nuclei, and throughout the reticular formation. In accordance with the well-known endocrine function of TRH, TRH-R1 is found predominantly expressed in hypothalamic regions. Expression of TRH-R1 in various brainstem nuclei and spinal cord motoneurons seems to be associated with the described effects of TRH on the vegetative and autonomic system as well as on the somatomotor system. Furthermore, the fully complementary expression of both receptor subtypes, even in regions where transcripts for both receptors were found (e.g., medial septum, lateral hypothalamus superior colliculi, substantia nigra, etc.), indicates that in discrete neuroanatomical pathways the two receptors serve highly specific functions for the transmission of TRH signals. Together with TRH-DE, the putative terminator of TRH actions that shows in various, but not all, brain areas, an overlapping mRNA distribution pattern with both receptors, the distribution of TRH-R2 mRNA seems to provide the anatomical basis for the described effects of TRH on higher cognitive functions as well as its effect on arousal, locomotor activity, and pain perception.

Aminopeptidases↗

Synthesis, cyclic voltammetry, and photophysical properties of a bridged o-phenylenediamine-C(60) dyad.

The synthesis, complete spectroscopic characterization, cyclic voltammetry, and photophysical measurements of a new o-phenylenediamine-C(60) dyad are described. By using a tether strategy, only a single regioisomer was obtained. Cyclic voltammetry measurements indicate that the two electroactive groups do not interact in their singlet ground states. Photophysical investigations reveal a rapid photoinduced electron transfer between the singlet excited state of the fullerene acceptor and the o-phenylenediamine donor, yielding a charge-separated radical pair.

Journal Article↗

Kinetic investigation of the specificity of porcine brain thyrotropin-releasing hormone-degrading ectoenzyme for thyrotropin-releasing hormone-like peptides.

Evidence indicates that neuronally released thyrotropin-releasing hormone (TRH) is selectively inactivated by TRH-degrading ectoenzyme (TRH-DE) (EC ). TRH-DE inhibitors may be used to enhance the therapeutic actions of TRH and to investigate the functions of TRH and TRH-DE in the central nervous system. Although TRH-DE appears to exhibit a high degree of specificity toward TRH, systematic specificity studies, which would facilitate inhibitor design, have not been previously conducted for this enzyme. In this paper we present the first description of TRH-DE specificity across a directed peptide library in which the histidyl (P(1)') residue of TRH was replaced by a series of amino acids. Peptides were synthesized using standard solid phase chemistry. Kinetic parameters were measured either by continuous or discontinuous fluorometric assays or by quantitative high pressure liquid chromatography. The P(1)' residue was found to influence significantly both the ability of the peptides to bind to TRH-DE, as measured by their K(i) values, and the ability of TRH-DE to catalyze their hydrolysis. Moderately bulky, uncharged P(1)' residues were found to bind preferentially to TRH-DE. Results from this screen provide valuable information for the development of TRH-DE inhibitors and have led to the identification of two potent, reversible TRH-DE inhibitors, l-pyroglutamyl-l-asparaginyl-l-prolineamide (K(i) = 17.5 micrometer) and Glp-Asn-Pro-7-amido-4-methyl coumarin (K(i) = 0.97 micrometer).

Aminopeptidases↗

Quantitative FISH analysis and in vitro suspension cultures of erythroid cells from maternal peripheral blood for the isolation of fetal cells.

Several techniques for the enrichment of nucleated fetal red blood cells present in maternal blood have been reported. Here we describe the use of a quantitative fluorescence in situ hybridization (FISH) method and in vitro suspension cultures of erythroid cells from newborn cord blood and maternal peripheral blood. Together with a rapid high performance liquid chromatography (HPLC) method, that allows us to determine as few as 100 cells containing haemoglobin F (HbF), we have scrutinized the reported enrichment methods for fetal nucleated cells in peripheral maternal blood. One hundred FISH analyses on maternal peripheral blood were performed. The method comprises a cell lysis method for depletion of red cells with minimal losses of nucleated cells, uniform numbers of cells (750 000 cells each) on microscopic slides, and inclusion of internal controls to monitor the efficacy of hybridization. Twenty-six cultures of pure erythroid progenitor cells from maternal peripheral blood were analysed for the expansion of fetal cells. To generate these in vitro cultures, nucleated cells from 10-20 ml of peripheral blood from 26 pregnant women were grown in media containing growth factors and hormones to yield over 10(7) of immature erythroid cells within two weeks. Of those, 13 cultures were from pregnancies with confirmed male fetuses. A total of approximately 8x10(8) maternal cells were added into tissue culture medium for these 13 cultures, resulting in about 2x10(8) nearly pure erythroid cells after two weeks. Whereas fetal cells, alone or added into cultures of peripheral blood, grow rapidly and can be detected quantitatively, we could not find any fetal cells in cultures from maternal blood. Likewise, in 7.5x10(7) peripheral blood cells probed by FISH analysis (half of which were from pregnancies with male fetuses) no single Y chromosome was detected. In summary, suspension cultures of erythroid cells can be established routinely and easily. With the quantitative FISH technique used, 750 000 cells per slide can be screened reliably for cells with Y chromosomes. However, the stringent quality-criteria and most elaborate methods indicate that fetal cells in maternal peripheral blood can not be found using the current technology.

Cell Culture Techniques↗

Do we need new indications for ECMO in neonates pretreated with high-frequency ventilation and/or inhaled nitric oxide?

OBJECTIVE: High-frequency ventilation (HFV) and/or inhaled nitric oxide (iNO) has reduced ECMO in neonates. But, frequently, improvement with HFV/iNO is temporary and only prolongs lung injury without preventing ECMO. We tried to identify a threshold oxygenation index (OI) that predicts temporary or persistent improvement with HFV/iNO in neonatal ECMO candidates as early as possible. DESIGN: Cohort study of all neonates with OI > 40 during intermittent positive pressure ventilation between 1992 and 1997. The first treatment was HFV; at an OI > 40 during HFV, iNO was added; at an OI > 40 during HFV+iNO, ECMO was initiated. Temporary improvement was defined as secondary need for ECMO or fatal chronic lung disease without ECMO. SETTING: University hospital level III neonatal intensive care unit. MAIN RESULTS: Ten of the 34 neonates studied rapidly required ECMO despite HFV/iNO. Eleven neonates temporarily improved for 1-10 days before the OI was again > 40. Nine received ECMO, two were denied ECMO after mechanical ventilation > 14 days and died of chronic lung disease. Thirteen neonates persistently improved with HFV/iNO without ECMO. The OI before, at 24 h or 48 h of HFV/iNO did not predict temporary or persistent improvement. However, after 72 h of HFV/iNO, neonates with persistent improvement had lower OIs than those with temporary improvement [median OI 16 (4-24) vs 31 (20-40); P = 0.0004]. In all neonates with an OI > or = 25 after 72 h, HFV/iNO eventually failed (positive predictive value 100%, sensitivity 91 %, specificity 100%, positive likelihood ratio 91). CONCLUSION: For neonates pretreated with HFV/iNO, an OI > 40 is an inadequate ECMO indication. Based on our data we hypothesize that an OI > or = 25 after 72 h of HFV/ iNO is a better ECMO indication that avoids prolonged barotrauma.

Administration, Inhalation↗

A molecular analysis of ground sloth diet through the last glaciation.

DNA was extracted from five coprolites, excavated in Gypsum Cave, Nevada and radiocarbon dated to approximately 11 000, 20 000 and 28 500 years BP. All coprolites contained mitochondrial DNA sequences identical to a DNA sequence determined from a bone of the extinct ground sloth Nothrotheriops shastensis. A 157-bp fragment of the chloroplast gene for the large subunit of the ribulosebisphosphate carboxylase (rbcL) was amplified from the boluses and several hundred clones were sequenced. In addition, the same DNA fragment was sequenced from 99 plant species that occur in the vicinity of Gypsum Cave today. When these were compared to the DNA sequences in GenBank, 69 were correctly (two incorrectly) assigned to taxonomic orders. The plant sequences from the five coprolites as well as from one previously studied coprolite were compared to rbcL sequences in GenBank and the contemporary plant species. Thirteen families or orders of plants that formed part of the diet of the Shasta ground sloth could be identified, showing that the ground sloth was feeding on trees as well as herbs and grasses. The plants in the boluses further indicate that the climate 11 000 years BP was dryer than 20 000 and 28 500 years BP. However, the sloths seem to have visited water sources more frequently at 11 000 BP than at earlier times.

Animals↗