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Biomedical subjects

A Schulze

Publications and source records attributed to A Schulze.

At least 109 records · Page 6Linked to original sources
PubMed1996

Effects of ventilator resistance and compliance on phrenic nerve activity in spontaneously breathing cats.

This study investigates the effects of respiratory mechanical loading and unloading on phrenic nerve activity and ventilation. Ten adult cats were anesthetized, intubated, and connected to a servocontrolled infant ventilator while breathing spontaneously in continuous positive airway pressure mode. The ventilator was then set to decrease the pressure at the airway opening in proportion to the inspiratory airflow or the volume of spontaneous breathing (resistive or elastic loading) or to increase the pressure at the airway opening accordingly (resistive or elastic unloading, also called proportional assist ventilation). When compared with continuous positive airway pressure, both resistive and elastic loading increased the number of phrenic nerve impulses per breath and the mean frequency of impulses (p < 0.01, ANOVA). In contrast, elastic unloading decreased phrenic nerve activity significantly in normal and injured lungs. Resistive unloading in normal lungs did not change phrenic nerve activity significantly. The compensatory response in phrenic nerve activity was not large enough to completely offset effects of loading and unloading on ventilation: elastic and resistive loading decreased ventilation. Unloading had the opposite effect on ventilation, particularly in injured lungs. We conclude that respiratory mechanical loading and unloading have statistically significant, opposite effects on phrenic nerve activity and opposite effects on ventilation.

Airway Resistance↗
PubMed1995

Protonation of histidine-132 promotes oligomerization of the channel-forming toxin aerolysin.

Aerolysin is a bacterial toxin that binds to a receptor on eukaryotic cells and oligomerizes to form stable, SDS-resistant, noncovalent oligomers that insert into the plasma membrane and produce well-defined channels. Little is known about the mechanisms controlling this process. Here we show that the protonation of a single histidine is required for oligomerization of aerolysin in solution. First we have investigated the effect of pH on the activity of aerolysin. The toxin's ability to disrupt human erythrocytes declined as the pH increased above 7.4. Experiments with receptor-free planar lipid bilayers demonstrated that the rate at which aerolysin formed channels also decreased with increasing pH, although the conductance of preexisting channels was not affected. The reduction in the rate of channel formation was shown to be due to a decrease in the toxin's ability to oligomerize. Our data indicate that the pH effect on activity is due to the deprotonation of a single residue rather than a global effect of pH on the protein. In agreement with our previous site-directed mutagenesis studies, His-132 is most likely to be the target of this pH effect. This conclusion was reinforced by the fact that we could shift the pH dependence of the activity to lower pH values by mutating Asp-139, a residue less than 3 A away from His-132 and likely to contribute to the usually high pKa of this histidine.

Bacterial Toxins↗
PubMed1995

Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site.

Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4.

3T3 Cells↗
PubMed1995

[Comparison of dietary surveys in Germany and Great Britain regarding objectives, methodology and results].

Referring to the data of the National Food Consumption Study in Germany and the Dietary and Nutritional Survey of British Adults, this article compares the food intake of German and British adults. Such a comparison is possible because both studies have mainly the same methodology. The comparison of the food intake of German and British adults points out food groups which Germans consume in higher amounts than British people do. To this category belong meat products and sausages, eggs, cheese and cottage cheese, butter, fat for cooking and salad oil, bread and pastries, vegetables, fruit, preserves and soft drinks. The Germans consume less meat, fish and fish products, milk and milk products, pasta, rice and miscellaneous cereals, potatoes, sugar, sweets and tea than the British people do. The consumption of fruit products, alcoholic beverages and coffee is nearly the same in Germany and Great Britain.

Adolescent↗
PubMed1995

Effect of the arterial oxygenation level on cardiac output, oxygen extraction, and oxygen consumption in low birth weight infants receiving mechanical ventilation.

OBJECTIVE: To investigate the effects on oxygenation of targeting the higher versus the lower end of the currently recommended range for pulse oximetry (Spo2). DESIGN: Nonrandomized crossover trial with the use of within-subject comparisons (two-tailed paired t test). SETTING: Level III neonatal intensive care unit of a university hospital. PATIENTS: Twenty infants whose lungs were mechanically ventilated (mean +/- SD: birth weight, 1192 +/- 396 gm; gestational age, 28.7 +/- 2.7 weeks; age at time of study, 42 +/- 26 hours). INTERVENTIONS: The inspired oxygen concentration was adjusted to achieve Spo2 readings of 93% to 96% versus 89% to 92% (Ohmeda pulse oximeter) or 95% to 98% versus 91% to 94% (Nellcor oximeter). MEASUREMENTS: Cardiac output was measured by echocardiography, oxygen content of arterial blood samples by cooximetry, and oxygen consumption by indirect calorimetry. RESULTS: The inspired oxygen concentrations required to achieve the Spo2 target ranges were 39.8% +/- 8.3% versus 28.7% +/- 6.1% (p < 0.001). The respective arterial oxygen contents were 18.0 +/- 2.6 ml/dl versus 16.9 +/- 2.5 ml/dl (p < 0.001). Oxygen consumption was unchanged. In the lower-oxygen condition no compensatory increase in cardiac output was detected; thus the estimated mixed venous oxygen tension decreased and the oxygen extraction ratio increased. Venous admixture increased from 15% +/- 6% to 31% +/- 9% in the lower-oxygen condition (p < 0.001). CONCLUSIONS: The "low normal" Spo2 target range allowed for less oxygen exposure. No signs of mismatch between systemic oxygen delivery and demand could be detected.

Blood Gas Analysis↗
PubMed1995

Vibrio spp. secrete proaerolysin as a folded dimer without the need for disulphide bond formation.

Proaerolysin is an extracellular dimeric protein that is secreted across the inner and outer membranes of Aeromonas spp. in separate steps. To investigate the role of protein folding in the second step, one or more cysteine residues were introduced and the mutant proaerolysins were expressed in Aeromonas hydrophila and Aeromonas salmonicida, as well as Vibrio cholerae. Replacing Met-41 with Cys resulted in expression of a protein that could form a dimer in which the monomers were linked together by a disulphide bridge. A double mutant was also made, in which Gly-202 and Ile-445 were replaced with cysteine in order to allow the formation of an intrachain disulphide bridge when the molecule was correctly folded. The M41C covalent dimer and G202C/I445C proaerolysin with the new intrachain bridge were both easily detected inside the bacteria, and they later appeared in the culture supernatants. Small amounts of incorrectly folded proaerolysin were also observed in the cells, but they were not secreted. We observed in the cells, but they were not secreted. We conclude that proaerolysin folds and dimerizes before being released from the cell, and that correct folding is a requirement for secretion to occur. The proton ionophore CCCP reduced release of the folded proteins. Unoxidized protein was secreted by cells grown in beta-mercaptoethanol and by a dsbA mutant of V. cholerae, indicating that disulphide bond formation may not be essential for release.

Aeromonas↗
PubMed1995

Sequential activation of cyclin E and cyclin A gene expression by human papillomavirus type 16 E7 through sequences necessary for transformation.

To investigate E7-dependent biochemical changes which are involved in cellular transformation, we analyzed the influence of human papillomavirus type 16 (HPV-16) E7 on the expression of cell cycle regulatory proteins. Expression of E7 in established rodent fibroblasts (NIH 3T3), which was shown to be sufficient for transformation of these cells, leads to constitutive expression of the cyclin E and cyclin A genes in the absence of external growth factors. Surprisingly, expression of the cyclin D1 gene, which encodes a major regulator of G1 progression, is unaltered in E7-transformed cells. In transient transfection experiments, the cyclin A gene promoter is activated by E7 via an E2F binding site. In 14/2 cells, which were used as a model system to analyze the role of HPV-16 E7 in the transformation of primary cells, we observed rapid E7-dependent activation of cyclin E gene expression, which can be uncoupled from activation of the cyclin A gene, since the latter requires additional protein synthesis. E7-driven induction of cyclin E and cyclin A gene expression was accompanied by an increase in the associated kinase activities. Two domains of the E7 oncoprotein, which are designated cd1 and cd2, are essential for transformation of rodent fibroblasts. It is shown here that growth factor-independent expression of the cyclin E gene requires cd2 but not cd1, while activation of cyclin A gene expression requires cd1 function in addition to that of cd2. These data suggest that cyclin A gene expression is controlled by two distinct negative signals, one of which also restricts expression of the cyclin E gene. The ability of E7 to separately override each of these inhibitory signals, via cd1 and cd2, cosegregates with its ability to fully transform rodent fibroblasts. Unlike serum growth factors, E7 induces S-phase entry without activating cyclin D1 gene expression, in keeping with the finding that cyclin D1 function is not required in cells transformed by DNA tumor viruses.

3T3 Cells↗
PubMed1994

Plasmid DNA profiles of Acinetobacter baumannii: clinical application in a complex endemic setting.

OBJECTIVE: To study the epidemiological, microbiological, and clinical features of infections due to Acinetobacter baumannii in a complex endemic situation over an 18-month period and to determine the clinical usefulness of plasmid DNA analysis of A baumannii in epidemiological investigations. DESIGN: Review of medical and laboratory records. Antibiotic resistance patterns, biotyping, and plasmid profile analysis were used to characterize clinical and environmental isolates. Pulsed-field gel electrophoresis (PFGE) of chromosomal DNA was performed to verify results obtained with the other typing methods. SETTING: Four different intensive care units of an 800-bed tertiary care center in Cologne, Germany. RESULTS: 240 patients were colonized or infected with A baumannii during the study period. No seasonal variations were observed. The majority of isolates (53%) were recovered from the respiratory tract. Major infections occurred in 61 patients; these included 48 bacteremias and eight pulmonary infections. Five different epidemic strains were identified: one each was A baumannii biotype 2 and 6, and three were biotype 9. A baumannii biotype 9 accounted for the vast majority of isolates (88%), which were clustered into three epidemic strains demonstrating distinct plasmid profiles. Two of these were considered genetically related as shown by PFGE. Epidemic strains were multidrug resistant, being uniformly susceptible to imipenem only. An epidemiological investigation failed to identify any point source of infection. Barrier precautions and improved handwashing was instituted in three of the four units and significantly reduced the incidence of colonization and infection in these units. Attack rates remained unchanged, however, in the burns unit where control measures were not implemented. CONCLUSION: Acinetobacter strains representing multiple biotypes and plasmid types were present in this endemic setting. Multidrug resistance in A baumannii is an important concern. Plasmid DNA analysis proved to be useful in epidemiological typing of A baumannii strains and may serve as a complementary typing system to traditional epidemiological methods.

Acinetobacter↗
PubMed1994

Plasmid DNA fingerprinting of Acinetobacter species other than Acinetobacter baumannii.

During the last years Acinetobacter species have emerged as clinically significant pathogens. Most infections are nosocomially acquired and mainly due to Acinetobacter baumannii. Little is known about the epidemiology and clinical significance of unnamed Acinetobacter species 3 (the second most often encountered member of the genus Acinetobacter) and other Acinetobacter species such as A. johnsonii, A. junii, and A. lwoffii. Seventy-five clinical isolates of Acinetobacter species other than A. baumannii (Acinetobacter species 3, n = 37; A. johnsonii, n = 20; A. junii, n = 8; A. lwoffii, n = 10) recovered from 66 patients over a period of 12 months were analyzed by plasmid DNA fingerprinting. Plasmids were found in 84.4% of Acinetobacter species 3 isolates and in all A. johnsonii, A. junii, and A. lwoffii isolates. Strains harbored up to 15 plasmids each. Almost every isolate gave a unique plasmid pattern. With one exception, identical plasmid profiles were detected only in corresponding isolates recovered from blood cultures and intravascular catheters from a given patient. Plasmid DNA fingerprinting proved to be useful for typing Acinetobacter species other than A. baumannii. There was no evidence of patient-to-patient transmission or hospital outbreaks due to these species. This finding is in contrast to the results obtained in studies of the hospital epidemiology of A. baumannii.

Acinetobacter↗
PubMed1994

Comparison of four different methods for epidemiologic typing of Acinetobacter baumannii.

A set of 103 epidemiologically well-defined Acinetobacter baumannii isolates obtained from nine hospital outbreaks and 21 unrelated strains were characterized by pulsed-field gel electrophoresis (PFGE) of total genomic DNA digested with ApaI. Among outbreak strains, eight different patterns and five possible variants were identified by PFGE. Results were compared with those from traditional typing methods such as plasmid profile analysis, antimicrobial susceptibility, and biotyping. Plasmid analysis revealed six different and two related patterns; one outbreak strain lacked plasmids. A total of 16 of the 21 unrelated strains harbored plasmids and exhibited unique patterns. Epidemiologically unrelated strains were placed into only two biotypes and had similar antimicrobial susceptibility patterns but were clearly distinguished by PFGE. PFGE of A. baumannii chromosomal DNA yielded reproducible and easily readable results and showed excellent discriminatory power. However, plasmid profile analysis may provide a cost-effective first step in epidemiological typing of A. baumannii isolates obtained from well-defined hospital outbreaks.

Acinetobacter↗
PubMed1994

Modulation of cyclin gene expression by adenovirus E1A in a cell line with E1A-dependent conditional proliferation.

To investigate how adenovirus E1A controls cell proliferation, we have fused E1A to the hormone-binding domain of the human estrogen receptor (ER) and introduced the E1A-ER chimeric gene together with an activated ras gene into primary rat embryo fibroblasts. Cell lines derived from this transfection proliferate in an estrogen-dependent manner. Estrogen-dependent activation of E1A-ER led to a rapid induction of both cyclin E and cyclin A gene expression. In contrast, levels of cyclin D1 were strongly reduced by activation of E1A-ER. Similar changes in cyclin gene expression were observed when primary human fibroblasts were infected with wild-type adenovirus and when adenovirus E1A was stably expressed in NIH 3T3 cells. Our findings suggest that activation of cyclin A and E, but not D1, gene expression by E1A precedes and may be responsible for E1A-dependent cell proliferation. In contrast, we found that quantitative disruption of complexes between the E2F transcription factor and the retinoblastoma protein is not required for E1A-dependent S-phase entry.

Adenovirus E1A Proteins↗
PubMed1994

Activation of the E2F transcription factor by cyclin D1 is blocked by p16INK4, the product of the putative tumor suppressor gene MTS1.

The oncoprotein cyclin D1 binds to and activates cyclin-dependent kinase 4 (cdk4), whose activity is inhibited by p16INK4, the product of the putative tumor suppressor gene MTS1. Cyclin D1 controls the timing of S phase onset in mammalian cells. We show that cyclin D1 acts as a positive regulator of the transcription factor E2F. In particular, cyclin D1 overexpression leads to the activation of the dihydrofolate reductase (DHFR) gene promoter. Activation depends on the E2F binding site in the DHFR promoter, known to mediate its activation at the G1/S transition in vivo. Cyclin D1 can also activate the adenovirus E2 promoter via E2F. Both promoters are repressed by p16INK4 and this repression can be released by overexpression of cdk4. The data reported here support a direct role for cyclin D1 and its associated kinase in cell cycle regulation of E2F activity and S phase-specific gene expression. In addition, we show that both E2F sites bind complexes containing the retinoblastoma protein (pRB) and that in RB-deficient cell lines overexpression of cyclin D1 fails to activate E2F-dependent transcription, indicating that pRB may be involved in promoter activation.

3T3 Cells↗
PubMed1994

Measurement of functional residual capacity by sulfur hexafluoride in small-volume lungs during spontaneous breathing and mechanical ventilation.

We modified a sulfur hexafluoride (SF6) washout technique to allow functional residual capacity (FRC) determinations in small-volume lungs both during spontaneous breathing and controlled mechanical ventilation. This method facilitates measurements in subjects who attempt spontaneous breaths between ventilator-generated breaths. We wished to confirm the accuracy and precision of the measurements and the method's sensitivity to change. The method uses a pneumotach together with a fast, mainstream infrared SF6 sensor mounted between the endotracheal tube and the ventilator circuit. A low flow of pure SF6 is delivered into the constant gas flow of the ventilator circuit to wash in tracer gas at a concentration of less than 2%. The flow signal and the instantaneous SF6 concentration is processed on-line by a computer. The calibration of the SF6 sensor's nonlinear signal and the ability of the flow sensor to reflect flow values precisely near zero flow had a major impact on the accuracy of the FRC estimate. This accuracy was tested by comparing measured FRC values with a dummy lung's true FRC that was varied from 7 to 70 mL. The comparison differed by 0.7 +/- 3.2% (mean +/- SD; range, -5.1 to 7.8%). As a measure of reproducibility (precision) across 20 FRC determinations in five adult rabbits, the average coefficient of variation was 1.7% (range, 0.57 to 4.33%) during continuous positive airway pressure and 1.98% (range, 0.35 to 3.81%) during controlled mechanical ventilation. The method proved sensitive to changes in FRC related to changes in airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗