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Biomedical subjects

A Eberhard

Publications and source records attributed to A Eberhard.

At least 37 records · Page 2Linked to original sources
PubMed1996

Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs.

The Vibrio fischeri luminescence genes are activated by the transcription factor LuxR in combination with a diffusible signal compound, N-(3-oxohexanoyl) homoserine lactone, termed the autoinducer. We have synthesized a set of autoinducer analogs. Many analogs with alterations in the acyl side chain showed evidence of binding to LuxR. Some appeared to bind with an affinity similar to that of the autoinducer, but none showed a higher affinity, and many did not bind as tightly as the autoinducer. For the most part, compounds with substitutions in the homoserine lactone ring did not show evidence of binding to LuxR. The exceptions were compounds with a homocysteine thiolactone ring in place of the homoserine lactone ring. Many but not all of the analogs showing evidence of LuxR binding had some ability to activate the luminescence genes. None were as active as the autoinducer. While most showed little ability to induce luminescence, a few analogs with rather conservative substitutions had appreciable activity. Under the conditions we employed, some of the analogs showing little or no ability to induce luminescence were inhibitors of the autoinducer.

4-Butyrolactone↗
PubMed1996

CT appearance of pulmonary vasculitis in children.

OBJECTIVE: The aim of this study was to determine whether a CT pattern that may represent early or subtle changes of pulmonary vasculitis in children exists. MATERIALS AND METHODS: High-resolution CT scans of the chest for 107 children were retrospectively reviewed by two radiologists who were unaware of the original study findings. Chest CT scans (conventional) for another 54 children who had symptoms or a diagnosis of vasculitis also were reviewed. RESULTS: We identified hazy or fluffy centrilobular, perivascular densities in 10 children, two of whom had small airways disease and eight of whom had vasculitis (Wegener's granulomatosis [n = 5], systemic lupus erythematosus [n = 1], scleroderma-polymyositis overlap syndrome [n = 1], and Churg-Strauss syndrome [n = 1]). The latter eight children underwent 35 scans, 17 of which were positive for these perivascular densities. All positive scans were associated with active disease of new onset (5/17) or with clinical exacerbation of preexisting systemic disease (12/17). The positive scans also were associated with an elevated erythrocyte sedimentation rate (13/17) and biopsy evidence of vasculitis from a variety of sites, including the lungs (n = 1), kidneys (n = 7), oropharynx (n = 5), skin (n = 9), lymph nodes (n = 1), and myocardium (n = 2). The single lung biopsy showed an angiocentric inflammatory-hemorrhagic process. Of the five patients who had positive scans, underwent therapy, and then had repeat studies, four patients had scans revert to normal in association with inactive disease. The remaining patient whose scan did not normalize failed to respond to treatment. CONCLUSION: The fluffy centrilobular pattern likely represents subtle changes of pulmonary vasculitis. In the appropriate clinical setting, such a finding may obviate the need for a lung biopsy.

Adolescent↗
PubMed1995

A computer program for automatic measurement of respiratory mechanics in artificially ventilated patients.

A program for automatic and periodic determination of respiratory mechanics in artificially ventilated patients is described. Airway pressure and flow signals are obtained from the ventilator in the controlled ventilation mode with constant flow inflation and end-inspiratory pause. Periodically, the program records both signals for a given time and it delimits a ventilatory cycle and its components out of this record. Then, four mechanical parameters of the respiratory system are calculated: (1) Rinit, the resistance obtained with the end-inflation occlusion technique; (2) Ers, the elastance (inspiratory) calculated from the slope of the airway pressure profile during inflation; (3) tau, the expiratory time constant; (4) PEEP, the global positive end expiratory pressure. All parameter measurements have been evaluated in experimental conditions, and are in good agreement with reference values. The complete software includes the display of the signals and of the trends together with automatic disk file backups. An additional program allows one to display the trends again and to create table text files containing all the recorded data for further analysis. The system proved to work in ICU and anaesthesia patients with various ventilators.

Adult↗
PubMed1994

Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes.

In Pseudomonas aeruginosa the LasR protein is required for activation of lasB and several other virulence genes. A diffusible signal molecule, the P. aeruginosa autoinducer (PAI), produced by the bacterial cell and released into the growth medium, is required for activity of LasR. By cloning a lasB::lacZ fusion and a lasR gene under control of the lac promoter in Escherichia coli, we have developed a quantitative bioassay for PAI. We have used this assay to follow the purification of PAI from cell-free culture supernatant fluids in which P. aeruginosa or E. coli containing the P. aeruginosa gene required for autoinducer synthesis, lasI, had been grown. Chemical analyses indicated the purified material was 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)dodecanamide. To confirm this assignment, the compound was synthesized and the synthetic compound was shown to have chemical and biological properties identical to those of PAI purified from culture supernatant fluids. The elucidation of the PAI structure suggests therapeutic approaches toward control of P. aeruginosa infections.

Bacterial Proteins↗
PubMed1994

Hypoprothrombinemia in childhood systemic lupus erythematosus.

Three children with systemic lupus erythematosus who developed hemorrhagic tendencies as a consequence of a clotting factor II (prothrombin) deficiency are described. All three responded rapidly to treatment with corticosteroids. A literature review added 25 case reports, with the following findings. First, factor II deficiency occurs in the presence of the lupus anticoagulant, although the interrelationship between the two is not understood. Second, the deficiency is presumed to be secondary to rapid clearing of the antigen/antibody factor II complex in the liver. Finally, most cases respond to corticosteroid therapy with or without the coadministration of vitamin K or fresh frozen plasma. In corticosteroid-dependent patients, the addition of antimetabolites such as azathioprine has enabled reduction in steroid doses.

Adolescent↗
PubMed1992

Theoretical analysis of occlusion techniques for measuring pulmonary capillary pressure.

We have developed a model including three serial compliant compartments (arterial, capillary, and venous) separated by two resistances (arterial and venous) for interpreting in vivo single pulmonary arterial or venous occlusion pressure profiles and double occlusion. We formalized and solved the corresponding system of equations. We showed that in this model 1) pulmonary capillary pressure (Pc) profile after arterial or venous occlusion has an S shape, 2) the estimation of Pc by zero time extrapolation of the slow component of the arterial occlusion profile (Pcao) always overestimates Pc, 3) symmetrically such an estimation on the venous occlusion profile (Pcvo) always underestimates Pc, 4) double occlusion pressure (Pcdo) differs from Pc. We evaluated the impact of varying parameter values in the model with parameter sets drawn either from the literature or from arbitrary arterial and venous pressures, being respectively 20 and 5 mmHg. Resulting Pcao-Pc differences ranged from 0.4 to 5.4 mmHg and resulting Pcvo-Pc differences ranged from -0.3 to -5.0 mmHg. Pcdo-Pc was positive or negative, its absolute value in general being negligible (< 1.1 mmHg).

Animals↗
PubMed1992

Exocrine pancreatic function in children with systemic lupus erythematosus.

We examined the incidence and spectrum of pancreatic disease in pediatric systemic lupus erythematosus (SLE). We measured serum immunoreactive cationic trypsinogen (IRT) in 185 samples obtained from 35 patients with SLE. Fifteen patients (43%) had elevated IRT levels on at least one occasion. Serum samples were obtained in 20 of 35 patients before start of treatment. Seven of these 20 patients (35%) had elevated IRT levels at diagnosis, which slowly returned to normal as their disease was controlled with treatment. A further 3 of these 20 patients in whom we had sera at diagnosis had elevated levels at some course during their illness. Of the remaining 15 patients in whom sera was not available at diagnosis, 5 patients had increased IRT levels on at least one occasion. We show that elevated IRT levels are common in pediatric SLE, but there was no apparent association with drugs such as prednisone and azathioprine. However, high levels of IRT at the time of diagnosis may be related to an underlying disease component such as vasculitis.

Adolescent↗
PubMed1991

Bowel perforation and interstitial cystitis in childhood systemic lupus erythematosus.

A 13-year-old girl presented with abdominal pain, fever, dysuria, incontinence and pyuria and was subsequently diagnosed as having systemic lupus erythematosus (SLE) with extensive gastrointestinal involvement and an associated interstitial cystitis. Despite aggressive therapy with high dose prednisone and cyclophosphamide she developed a small bowel perforation and subsequently died. The combination of bowel symptoms and interstitial cystitis seems unique to the population with SLE, while the separate complication of bowel perforation carries an extremely poor prognosis in this group of patients.

Adolescent↗
PubMed1989

Outcomes following the use of rational guidelines in the management of jaundiced newborn infants.

In 1975, rational guidelines for management of the jaundiced newborn infant were introduced to the Mercy Maternity Hospital, Melbourne. The guidelines were produced as four charts, each chart covering a particular birthweight range. The charts have been used widely. The effect of introduction of the charts has been examined by comparing the years 1971-74 with 1975-77. An overall decrease occurred in the use of phototherapy, without an increase in the use of exchange transfusion or in those with a serum bilirubin level above 339 mumol/L. The difference was not explained by an alteration in the spectrum of causes of jaundice. Long-term follow-up of jaundiced infants managed according to these guidelines revealed a satisfactory outcome despite a significant reduction in active treatment. The associated avoidance of potential side effects of treatment of the jaundiced newborn infant warrants consideration of the use of these charts by other neonatal units.

Exchange Transfusion, Whole Blood↗
PubMed1986

Analogs of the autoinducer of bioluminescence in Vibrio fischeri.

The enzymes for luminescence in Vibrio fischeri are induced only when a sufficient concentration of a metabolic product (autoinducer) specifically produced by this species accumulates. It has previously been shown that the autoinducer is 3-oxohexanoyl homoserine lactone and that it enters the cells by simple diffusion. To further study the mechanism of induction, we have synthesized several analogs of the autoinducer. The analogs were tested with V. fischeri for their inducing activity and for their ability to inhibit the action of the natural autoinducer. The compounds were found to display various combinations of inducing and inhibiting abilities. None of the compounds tested appeared to have any effect on cells of V. harveyi strain MAV or Photobacterium leiognathi strain 721, but several of the compounds decreased light output by P. phosphoreum strain 8265. These studies show that 1) the site of action of the autoinducer is not highly sterically constrained 2) the autoinducers of other species of luminous bacteria are likely to be quite different from that of V. fischeri and 3) a simple mode in which one autoinducer molecule binds to a single receptor protein site and thus initiates luciferase synthesis is inadequate. The analogs should prove useful in the study of the binding site and mode of action of the autoinducer.

4-Butyrolactone↗
PubMed1986

A program for cycle-by-cycle shape analysis of biological rhythms. Application to respiratory rhythm.

A computer program for cycle-by-cycle analysis and quantification of biological rhythms, written for an Apple II microcomputer with 48k RAM is described. The program comprises 4 steps: (1) file constitution suitable for biological data collecting; (2) signal digitalization at a sampling rate up to 1 kHz with storage in central memory; (3) determination of each cycle's limits (delimitation parameters being defined by the user; following delimitation, cycles may be dropped or saved for further analyses); (4) cycle-by-cycle harmonic analysis (fast Fourier Transform algorithm). The program is written in BASIC Applesoft, hardware-dependent functions (analog inputs, graphic display and random access disk storage) are implemented in subroutines (partly assembler) which may be easily modified. The program, consisting of 4 chained procedures is run interactively, although procedure (4) may be run automatically. Analysis of human ventilatory airflow signal with this program is given as an example of cycle-by-cycle shape analysis of a biological rhythm.

Humans↗
PubMed1981

Structural identification of autoinducer of Photobacterium fischeri luciferase.

Synthesis of bacterial luciferase in some strains of luminous bacteria requires a threshold concentration of an autoinducer synthesized by the bacteria and excreted into the medium. Autoinducer excreted by Photobacterium fischeri strain MJ-1 was isolated from the cell-free medium by extraction with ethyl acetate, evaporation of solvent, workup with ethanol-water mixtures, and silica gel chromatography, followed by normal-phase and then reverse-phase high-performance liquid chromatography. The final product was greater than 99% pure. The structure of the autoinducer as determined by high-resolution 1H nuclear magnetic resonance spectroscopy, infrared spectroscopy, and high-resolution mass spectrometry was N-(3-oxohexanoly)-3-aminodihydro-2(3H)-furanone [or N-(beta-ketocaproyl)homoserine lactone]. The formation of homoserine by hydrolysis of the autoinducer was consistent with this structure. Synthetic autoinducer, obtained as a racemate, was prepared by coupling homoserine lactone to the ethylene glycol ketal of sodium 3-oxohexanoate, followed by mildly acidic removal of the protecting group; this synthetic material showed the appropriate biological activity.

4-Butyrolactone↗
PubMed1980

[Clinical chemical diagnosis of affective diseases by means of a neuroendocrine function test (author's transl)].

The stimulation of pituitary hormone secretion with thyroliberin and by insulin-induced hypoglycemia was investigated on 52 depressive patients and 12 postdepressive, lithiumtreated subjects. The serum concentrations of somatotropin, cortisol, prolactin, thyrotropin and glucose were followed for 2 hours. Differences in the neuroendocrine response between endogenous and reactive (neurotic) depressive patients were observed, and changes during the course of the diseases were also recorded. 1. Stimulation of somatotropin and cortisol secretion, and the decrease of glucose are diminished in endogenous depressive patients, as compared to those of reactive depressive patients and healthy controls. 2. Somatotropin stimulation maxima below 40 mU/l in depressive phase are indicative of endogenous depression, rather than the reactive form, with a confidence probability of 0.9. 3. An increase in the stimulation of somatotropin and cortisol secretion can be shown after termination of endogenous depression. However, the somatotropin maxima are then also lower than those found in reactive depression. 4. The stimulation of somatotropin secretion in lithiumtreated psychosis-free subjects shows no difference from that of healthy controls; thyrotropin secretion increase. The weak, insulin-induced hypoglycemia, observed in these subjects, is higher (66%) than in the healthy controls. 5. Fear and agitation have an inhibitory effect on the stimulation of the prolactin secretion during the depressive phase. The pituitary stimulation test offers a means of ascertaining the disturbed neuroendocrine function in affective diseases and objectifying the differential diagnosis of depressive syndromes.

Adjustment Disorders↗
PubMed1978

Clinical investigation of the menstrual cycle. II. Neuroendocrine investigation and therapy of the inadequate luteal phase.

Nonhormonal drugs--diphenylhydantoin and nialamide, which act on the central nervous system and have no known endocrine activity--were given to two groups of women with distinct types of electroencephalographic patterns in an effort to regulate menstrual disorders. Equalization of the lengths of both the follicular phase and the luteal phase to the normal range was observed during the drug therapy. Forty-five per cent of the pregnancy rate was achieved in 36 of the 80 infecund patients within 4 months of treatment. The mode of action of these drugs is still unknown.

Adult↗
PubMed1977

[Neuroendocrine investigation of the follicular phase: spontaneous and after estrogen stimulation (author's transl)].

Estrogen stimulation on days 7, 8, 9 of the menstrual cycle induces disturbances of the usual clinical and hormonal patterns. Alpha rythm (8-12 Hz) variation curve, studied by mathematical analysis, is modified, and delayed ovulation happened at its nadir. It is concluded that EEG appears as a tool for clinical neuroendocrine correlations and that this preliminary study may indicate that this estrogen positive feedback is received at the neurovegetative level.

Alpha Rhythm↗