Biomedical subjects

J Sauer

Publications and source records attributed to J Sauer.

At least 37 records · Page 2Linked to original sources

PubMed1999

Multiple-task performance on a computer-simulated life support system during a space mission simulation.

This paper presents an experiment which examined the effects of isolation and confinement during a simulation of a short-term space mission. During the 7-day spaceflight simulation, four Canadian astronauts were tested daily on a 30-min performance task. The task, CAMS (Cabin Air Management System), represents a computer-based simulation of a generic life support system. As a multiple-task environment, it allows the measurement of a wide range of task management variables such as primary and secondary task performance, and system control activities. Measures of subjective state variables were also taken. The results did not show any evidence of serious performance decrements for any crew member. The analysis revealed different adjustment patterns with which crew members responded as a function of mission duration and variations in workload. Among the secondary tasks employed, prospective memory was found to be more sensitive than reaction time to increases in workload. The paper concludes with a discussion of the utility of spaceflight simulations and computer-based simulations of space work.

Adaptation, Psychological↗

PubMed1999

Expression of the Methanobacterium thermoautotrophicum hpt gene, encoding hypoxanthine (Guanine) phosphoribosyltransferase, in Escherichia coli.

The hpt gene from the archaeon Methanobacterium thermoautotrophicum, encoding hypoxanthine (guanine) phosphoribosyltransferase, was cloned by functional complementation into Escherichia coli. The hpt-encoded amino acid sequence is most similar to adenine phosphoribosyltransferases, but the encoded enzyme has activity only with hypoxanthine and guanine. The synthesis of the recombinant enzyme is apparently limited by the presence of the rare arginine codons AGA and AGG and the rare isoleucine AUA codon on the hpt gene. The recombinant enzyme was purified to apparent homogeneity.

Amino Acid Sequence↗

PubMed1999

Performance evaluation in analogue space environments: adaptation during an 8-month Antarctic wintering-over expedition.

BACKGROUND: This paper reports a study which examined the impact of long-term isolation and confinement on multiple-task performance. METHODS: A group of 10 scientists and 6 technicians from a French wintering-over expedition in the Antarctic participated in the 8-mo study. The group was tested 8 times on a computerized simulation of a complex life support system. The task environment allowed the measurement of primary and secondary task performance, system control activities and subjective operator state. RESULTS: No signs of serious performance decrements were observed but a number of subtle indications of hidden decrements emerged. The data also revealed strong differences in performance between the professional groups. Finally, the paper discusses the implications of the work for extended spaceflight.

Adult↗

PubMed1999

Maintenance of complex performance during a 135-day spaceflight simulation.

BACKGROUND: The maintenance of crew performance during extended space missions has been a major concern because of the problems associated with prolonged isolation and confinement. Previous research has failed to address this problem by not using appropriate performance tests. METHOD: Three Russian cosmonauts were tested on a PC-based simulation of a spacecraft's life support system during a 135-d simulation of a MIR spaceflight. A complex multiple-task environment was used to examine a comprehensive range of task management variables, including both primary and secondary task performance, control activity and information sampling behavior. Subjective state variables were also measured. RESULTS: The data suggested an overall successful adjustment to isolation and confinement, though some indications of temporary disruptions of some performance indicators were observed. Information sources were sampled less frequently with increasing mission length while system control activities showed a tendency to increase. CONCLUSION: Suggestions are made to address the problem of continuous learning during repeated testing sessions. Using well-designed computer simulations of complex task environments appears to be a promising approach for the evaluation of crew member performance.

Adult↗

PubMed1998

Cytokine expression and molecular mechanisms of their auto/paracrine regulation of anterior pituitary function and growth.

The pituitary gland expresses cytokines and their receptors. IL-2 receptor transcripts and protein products are co-localized in ACTH-, PRL-, and GH-producing cells (double immunofluorescence). IL-2 and IL-6 (1-1000 IU/ml) are involved in the autocrine/paracrine regulation of normal and tumor (GH3 mammosomatotroph cell line and adenoma cell cultures) anterior pituitary hormone-producing cell growth (cell number, DNA synthesis, c-fos mRNA expression and autoradiography combined with hormone staining). IL-1 regulates the growth of normal pituitary cells but does not act on GH3 cells. IL-1ra, which blocks this action, is expressed in tumoral pituitary (mainly GH- and ACTH-) cells. In ACTH- cells, IL-1 enhances glucocorticoid feedback, stimulating glucocorticoid response element transcriptional activity. Cytokines, through specific functional receptors, act as inter/auto-cellular factors that regulate not only the function but also the growth of anterior pituitary cells.

Animals↗

PubMed1998

The Th1 and Th2 cytokines IFN-gamma and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: involvement of IL-1.

Monocytes express IL-1 and IL-1 receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS). IL-1 self-induction contributes to the increase in IL-1 following LPS stimulation. LPS-stimulated IL-1 and IL-1Ra production are inhibited by glucocorticoids. In the present work we examined the regulation of IL-1Ra by Th1 cytokine IFN-gamma, Th2 cytokine IL-4, glucocorticoids and IL-1 in human monocytes. We demonstrate that IL-1 contributes to LPS-induced IL-1 Ra expression as shown by IL-1 blockade in LPS-stimulated monocytes using a specific anti-IL-1beta antibody or recombinant IL-1Ra. Glucocorticoids inhibited IL-1beta-stimulated IL-1Ra mRNA expression and protein production. Glucocorticoids inhibited both IL-1-mediated and non-mediated LPS stimulation of IL-1Ra expression. Both IFN-gamma and IL-4 reversed the inhibitory effect of glucocorticoids on IL-1Ra expression and secretion. The effect of IFN-gamma was blocked by pretreatment of monocytes with an anti-IL-1beta blocking antibody, whereas the effect of IL-4 could not be blocked, demonstrating that IFN-gamma acts through a mechanism dependent on endogenous IL-1 production, whereas IL-4 acts through an IL-1-independent one. Consistent with this finding, IFN-gamma (but not IL-4) failed to reverse the inhibitory effect of glucocorticoids when stimulated by IL-1, and only IL-4 combined with IL-1 showed synergism resulting in an increase in IL-1 Ra production. The differential regulation and involvement of IL-1 in the expression of IL-1Ra by IFN-gamma, IL-4 and glucocorticoids sets the level of monocyte responsiveness during the Th1 or Th2 responses.

Glucocorticoids↗

PubMed1998

Task analysis for the investigation of human error in safety-critical software design: a convergent methods approach.

An investigation was conducted into sources of error within a safety-critical software design task. A number of convergent methods of task- and error-analysis were systematically applied: hierarchical task analysis (HTA), error log audit, error observation, work sample and laboratory experiment. HTA, which provided the framework for the deployment of subsequent methods, revealed possible weaknesses in the areas of task automation and job organization. Application of other methods within this more circumscribed context focused on the impact of task and job design issues. The use of a convergent methods approach draws attention to the benefits and shortcomings of individual analysis methods, and illustrates the advantages of combining techniques to analyse complex problems. The features that these techniques should possess are highlighted.

Ergonomics↗

PubMed1998

Interleukin-1 beta enhances interleukin-1 receptor antagonist content in human somatotroph adenoma cell cultures.

In addition to the well-known modulation of immune and inflammatory responses, the interleukin-1 (IL-1) system has been shown to be involved in the regulation of anterior pituitary hormone secretion and growth. We previously demonstrated that IL-1 receptor antagonist (IL-1ra) is expressed in human pituitary adenomas cultured in vitro. In the present study, we investigated the regulation of IL-1ra protein by IL-1 beta (1-100 U/mL) in human somatotroph adenomas (n = 9) cultured for 12-48 h. IL-1 beta significantly enhanced the concentration of IL-1ra dose dependently in the somatotroph adenoma cell lysates, whereas IL-1ra concentrations remained unchanged in the culture supernatants. Furthermore, basal IL-1ra concentrations were significantly higher in the cell lysates compared with the corresponding culture supernatants. The regulation of IL-1ra in somatotroph adenoma cells is different from human cultured monocytes, in which IL-1 beta significantly stimulated IL-1ra secretion into the culture supernatants, and no change of intracellular IL-1ra content was observed. Incubation of the somatotroph adenoma cells with 100 U/mL IL-1 beta did not result in a change of GH concentrations in the culture supernatants. Enhancement of intracellular IL-1ra protein by IL-1 beta may represent a mechanism intrinsic to somatotroph adenoma cells to counterregulate the response to IL-1 beta on hormone secretion or cellular growth.

Adenoma↗

PubMed1998

Effects of sleep deprivation and user interface on complex performance: a multilevel analysis of compensatory control.

This study was carried out to test the compensatory control model, which predicts performance maintenance under stress at the expense of effort and increased selectivity. It examined the effects of sleep deprivation on performance in an automated process control task based on a simplified life support system with two types of operator control panel interface: machine centered (M-C), in which access to the system was scheduled by the computer, and human-centered (H-C), in which access was ad-lib. The task environment also permitted the analysis of changes in strategy and in subsidiary activities (alarm reaction time, prospective memory). In a 2 x 2 repeated-measures design, 16 participants carried out the task with each interface after both normal sleep and one night of sleep deprivation (SD). No effects of SD were observed on primary task performance. As predicted, SD effects were confined to strategy changes and subsidiary task impairment and occurred only under the (low control) M-C interface. Subjective effort was increased under SD, with greater increases of effort associated with high levels of performance protection. The findings provide strong evidence in favor of the compensatory control model and argue for the use of complex, multilevel tasks in the analysis of performance under stress. Actual or potential applications include the development of more sensitive performance-testing systems based on multilevel analysis of decrement, and the design of interfaces for shift work and other suboptimal work conditions.

Adult↗

PubMed1998

[A methodological study in a space flight simulation context].

To study the effects of isolation and confinement on small groups during long space flights, it is habitual to use closed hyperbaric ground chambers. For the first time, the European Space Agency made use of a nautral environment taking advantage of an Antarctic winter-over at the French Dumont d'Urville Station. The main objective of that study ("International Antarctic Psychological Programme"), was to compare different Russian tests used for training cosmonauts to a W. European approach validated during previous winter studies and European ground chamber simulations. Russian techniques appeared to be oriented to a narrow range of phenomena and unsuited to discern the adjustment to stress conditions.

Adaptation, Psychological↗

PubMed1998

[Is graduate education for surgical specialist adequate? Results of a survey of surgical assistants in Berlin-Brandenburg].

A questionnaire was sent to all surgical registrars in Berlin and Brandenburg. The number of operations and other characteristic facts in surgical training were requested; 127 answers were sent back. The number of operations on colon, small intestine, stomach, and breast was not adequate to the required number of operations for specialist qualification in Berlin and Brandenburg. Although not representative, the inquiry shows a trend in surgical training.

Berlin↗

PubMed1997

Ab initio predictions of zeolite structures and 29Si NMR chemical shifts.

A recent shell-model potential parameterized on ab initio data is used for predicting the all-silica structures of zeolites MFI, MEI, MTW, TON, FAU and of alpha-quartz. Cluster models are defined around each site and the 29Si NMR shielding constants are calculated by ab initio techniques (GIAO-HF). Good agreement with observed 29Si NMR chemical shifts is found. Comparison is made with shifts calculated for observed structures. The structures predicted by the ab initio shell-model potential prove as accurate as the observed ones when judged on the quality of the calculated 29Si NMR spectra.

Isotopes↗

PubMed1996

Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human pituitary adenoma explants.

We have previously shown that interleukin-2 (IL-2) and IL-6, which are expressed in the anterior pituitary, affect anterior pituitary cell proliferation in normal rats and cell lines. Here we examined their effects on the c-fos expression by human anterior pituitary adenomas. Adenoma cells in culture do not express c-fos mRNA. In adenoma explants, however, c-fos expression was detected and was regulated by IL-2 or IL-6. In different tumors (ACTH-, PRL-, GH-secreting and non functioning adenomas), these interleukins had inhibitory or stimulatory effects but the kind of response does not seem to be associated to tumor type or size. Using blocking antibodies, we observed that intrinsic IL-2 and IL-6 regulate c-fos expression in the same way. Our data suggest that IL-2 and IL-6 are not only involved in the regulation of pituitary adenoma function but may also, given the role of c-fos in cell proliferation, be implicated in the development of human pituitary adenomas.

Adenoma↗

PubMed1996

Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids. TNF-alpha priming increases glucocorticoid inhibition of TNF-alpha-induced cytotoxicity/apoptosis.

Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-alpha increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via the glucocorticoid response elements (GRE) in L-929 mouse fibroblasts transfected with a glucocorticoid-inducible reporter plasmid. In addition, TNF-alpha also enhanced GR number. The TNF-alpha effect on transcriptional activity was absent in other cell lines that express TNF-alpha receptors but not GRs, and became manifest when a GR expression vector was cotransfected, indicating that TNF-alpha, independent of any effect it may have on GR number, has a stimulatory effect on the glucocorticoid-induced transcriptional activity of the GR. Moreover, TNF-alpha increased GR binding to GRE. As a functional biological correlate of this mechanism, priming of L-929 cells with a low (noncytotoxic) dose of TNF-alpha significantly increased the sensitivity to glucocorticoid inhibition of TNF-alpha-induced cytotoxicity/apoptosis. TNF-alpha and IL-1 beta had the same stimulatory action on glucocorticoid-induced transcriptional activity of the GR via the GRE, in different types of cytokine/glucocorticoid target cells (glioma, pituitary, epithelioid). The phenomenon may therefore reflect a general molecular mechanism whereby cytokines modulate the transcriptional activity of the GR, thus potentiating the counterregulation by glucocorticoids at the level of their target cells.

Animals↗

PubMed1996

Omission of the pelvic irradiation in stage I testicular seminoma: a study of postorchiectomy paraaortic radiotherapy.

PURPOSE: To review the survival, cure rate, and pattern of relapse or progression of patients with histologically confirmed Stage I testicular seminoma who underwent orchiectomy and radiation therapy to paraaortic lymphatics only. The pelvic ipsilateral lymph nodes were not irradiated. METHODS AND MATERIALS: Between 1978 and 1992, 150 patients with Stages I or II testicular seminoma received treatment at the Department of Radiation Oncology of the University of Wuerzburg. The distribution by stage was Stage I, 117 patients of which 93 were pT1 N0 M0 and 24 were pT2 N0 M0. Four patients were staged as Stage II (pT3 N0 M0), and in 29 patients the T Stage was not specified. Eighty-six patients from the 117 Stage I (pT1-pT2, N0 M0 according to the TNM classification) seminoma received postorchiectomy irradiation, and are analyzed for outcome in this article. The distribution of the Stage I patients by pT Stage was 71 pT1 and 15 pT2 patients. All these 86 patients had their paraaortic nodes (the biological target volume extending from top of L1 to the bottom of L5) irradiated with four field technique. Tumor dose was specified at normalization point along the central axis. The median tumor dose was 30 Gy given in 1.8-2.0 Gy fractions. Elective irradiation to the ipsilateral hemipelvis (iliac nodes) was totally abandoned. RESULTS: The 10-year disease-free survival and overall survival were 95.3 and 100%. No recurrence in the irradiated field was noted. Four patients (4.7%) experienced relapse of disease outside the treated volume. The most common site of solitary failure was the ipsilateral hemipelvis (one iliacal and one inguinal). One patient developed metastatic disease to the lung. One patient developed a mediastinal recurrence with superior vena cava syndrome and was successfully salvaged by mediastinal irradiation and chemotherapy. CONCLUSIONS: Recommendation for the future management of Stage I seminoma include: reduced biological target volume to the paraaortal lymph nodes (from lumbar vertebra L1 to L5). Complete elimination of irradiation to the pelvic nodes is warranted. Radiation dose should not exceed 30 Gy.

Adult↗

PubMed1996

Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men.

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. Twelve hours before both experiments, 10 of these subjects were pretreated with 300 micrograms G-CSF subcutaneously. G-CSF itself increased granulocyte and monocyte counts and the plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors (sTNF-R) p55, and p75 and interleukin-1 receptor antagonist (IL-1ra). G-CSF did not influence plasma IL-1 beta and IL-6 levels. In the G-CSF-pretreated subjects endotoxin-induced surges in rectal temperature and in the plasma levels of TNF-alpha plasma levels were about 50% increased, and surges in the plasma levels of both sTNF-Rs and IL-1ra were about twice as high as in the control group. Endotoxin-induced increases in IL-6, cortisol, and heart rate were not modified by G-CSF pretreatment. Endotoxin administration induced a transient 50% reduction in leukocyte counts in the G-CSF-pretreated subjects that was not seen in the control group. We conclude that a single stand dose of G-CSF increases the plasma levels of cytokines and cytokine receptors and considerably modifies the host response of healthy humans to a low dose of endotoxin.

Bacterial Toxins↗

PubMed1996

Syntheses and selective inhibitory activities of terphenyl-bisamidines for serine proteases.

Biphenyl nitriles 5a-c, terphenyl dinitriles 11a-d, and naphthalene-bis(benzonitrile) 11c were prepared by palladium-catalyzed cross coupling reactions and subsequently converted to biphenyl amidines 8a-c and bis(benzamidines) 4a-e. Among the biphenyl amidines 8 only the meta-derivative 8b inhibits factor Xa and trypsin (Ki = 10 microM). The terphenyl bisamidine 4c does not inhibit factor Xa, trypsin, thrombin, and plasmin, while 4a and 4d are almost equipotent inhibitors of these enzymes (Ki 1-6 microM), and 4b and 4e are selective for trypsin (Ki = 0.2 and 0.3 microM; but Ki > 1 microM for factor Xa, thrombin, and plasmin). X-ray analysis of crystals of 4b complexed with bovine trypsin revealed a unique binding mode: one benzamidino group binds in the S1 site to the side chain carboxylate of Arg189. The central phenyl group is twisted away from the S2/S3 sites and the second amidino group contacts the Asn143 side chain.

Amidines↗

PubMed1996

Skill maintenance in extended spaceflight: a human factors analysis of space and analogue work environments.

This paper discusses the implications of increasing mission lengths of manned spaceflight for the design of future space systems from a human factors point of view. It is argued that the increase in mission duration has brought about a number of new problems, which have not been sufficiently addressed in space research. Therefore, a review of analogue work environments is carried out to make up for the paucity of space research found in the area of human performance in long-duration spaceflight. This resulted in an evaluation of seven analogue environments concerning their similarity to space with industrial process control and nuclear submarines coming out as the closest match on the technical dimension. Finally, some recommendations are given from the lessons learned in spaceflight, simulation studies and appropriate analogue environments.

Aerospace Medicine↗