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Biomedical subjects

A Hutter

Publications and source records attributed to A Hutter.

14 recordsLinked to original sources

[Chronic fatigue in complementary rehabilitative medicine--predictors of the outcomes].

Chronic exhaustion and fatigue are increasingly important in rehabilitation medicine. Objectives of this study were (a) to describe the effects of in-patient rehabilitation on patients with chronic fatigue syndromes, (b) to identify predictors for treatment outcome, and (c) to analyze the impact of comprehensive diagnosing on these issues. A total of 171 patients with chronic exhaustion or fatigue (90 % female, mean age 55 +/- 10 yrs) from a rehabilitation hospital with a complementary medicine-based treatment concept were included in a prospective observational study. Within the longitudinal study patients were examined three times (on admission to hospital, at discharge as well as six months later). Participation rate of the postal inquiry was 69 %. Besides items constructed ad hoc, Patient questionnaires included the Symptom Checklist and assessment instruments for depression, quality of life, sense of coherence as well as for changes in experience and behaviour. Treatment outcome was defined as sum score of binary-coded response criteria. The pattern of complaints differed clearly between diagnostic subgroups (neurasthenia, affective disorders, adjustment disorders) before treatment. At discharge from hospital patients showed clinically relevant improvements lasting for six months after rehabilitation. Multiple regression analyses revealed a statistically significant relationship (R (mult) = 0.59) between predictors and outcome at discharge from hospital. A better result was associated with higher trust in treatment success, active information seeking on complementary medicine, healthier feeding habits, better somatic health and a decreased mental status, with regard to the status before treatment. The prediction of outcome after six months was comparably poorer (R (mult) = 0.42). Treatment success was higher in the absence of a diagnosis of neurasthenia, in patients accepting the group-oriented treatment concept and in patients not believing that their disease was due to their own way of living. Trust in the success of the treatment was a highly ranked predictor for longer lasting outcome, too. The results underline the importance of motivation aspects for treatment outcome indicating that individual expectations and attitudes should be considered in a more distinct way when allocating patients to rehabilitative programmes.

Complementary Therapies↗

Exploring redundancy in the yeast genome: an improved strategy for use of the cre-loxP system.

Gene families having more than three members are a common phenomenon in the Saccharomyces cerevisiae genome. As yeast research enters the post-genome era, the development of existing deletion strategies is crucial for tackling this apparent redundancy, hence a method for performing rapid multiple gene disruptions in this organism has been developed. We constructed three replacement cassettes in which different selectable markers were placed between two loxP loci. Multiple deletions (of members of a gene family) were generated, in one strain, using sequential integration of different replacement markers (kanMX, LYS2, KlURA3 and SpHIS5). Their excision from the genome was performed simultaneously, as the final step, using a new cre recombinase vector, which carries the cycloheximide-resistance gene from Candida maltosa as a selectable marker. Our multiple gene deletion system significantly accelerates and facilitates the functional analysis process and is particularly useful for studying gene families in either laboratory or industrial yeast strains.

Blotting, Southern↗

Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the components of the extracellular matrix (ECM). The balance between MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in the pericellular environment determines the most significant proteolytic events in tissue remodeling. In vitro evidence is accumulating that these molecules may be crucial in the maturation of neural cells. Here, we investigated the in vivo expression of MMPs 2, 3, and 9 and TIMPs 1, 2, and 3 in the developing and adult rat cerebellum using immunohistochemistry and in situ hybridization. During postnatal development, all Purkinje (PK) cell somata expressed all the MMPs and TIMPs studied, whereas their growing dendritic trees expressed only MMP 3 and TIMP 3. In the adult, MMP 3 was confined to PK cell bodies, whereas TIMP 3 was expressed in PK cell somata and processes. Irrespective of the developmental stage, Bergmann glial processes contained only MMP 9, but their somata contained both TIMP 1 and MMP 9. In granular cells, MMPs 3 and 9 and TIMPs 1, 2, and 3 were chiefly detected at a time when migration is known to be maximal; except for that of TIMP 1, their expression persisted in the internal granular layer in the adult. The functional relevance of MMP expression was verified by gelatin zymography. MMP 9 activity was maximal on postnatal day 10 (P10) and was detectable at a low level on P15 and in the adult, whereas MMP 2 activity remained similar throughout postnatal development. Regional and cell-specific expression of MMPs and TIMPs closely reflects the successive stages of cerebellar development, thereby suggesting a pivotal role for ECM proteolysis in brain development and plasticity.

Age Factors↗

Radon progeny unattached fraction in an atmosphere far from radioactive equilibrium.

It is often assumed that the unattached fraction of the exposure to suspended radon progeny activity can be predicted from particle concentration measurements. While this may be true in many circumstances, there are important exceptions to this rule. In particular, in an atmosphere far from radioactive equilibrium, such as a working area in a mine close to a source of radon and supplied with fresh air, the unattached fraction can be a factor of ten or more greater than indicated by a simple particle concentration measurement. Recent measurements made in a diesel powered uranium mine are presented to illustrate this effect.

Air Pollutants↗

Ethanol production using nuclear petite yeast mutants.

Two respiratory-deficient nuclear petites, FY23 delta pet191 and FY23 delta cox5a, of the yeast Saccharomyces cerevisiae were generated using polymerase-chain-reaction-mediated gene disruption, and their respective ethanol tolerance and productivity assessed and compared to those of the parental grande, FY23WT, and a mitochondrial petite, FY23 rho(0). Batch culture studies demonstrated that the parental strain was the most tolerant to exogenously added ethanol with an inhibition constant, Ki, of 2.3% (w/v) and a specific rate of ethanol production, qp, of 0.90 g ethanol g dry cells-1 h-1. FY23 rho(0) was the most sensitive to ethanol, exhibiting a Ki of 1.71% (w/v) and qp of 0.87 ethanol g dry cells-1 h-1. Analyses of the ethanol tolerance of the nuclear petites demonstrate that functional mitochondria are essential for maintaining tolerance to the toxin with the 100% respiratory-deficient nuclear petite, FY23 delta pet191, having a Ki of 2.14% (w/v) and the 85% respiratory-deficient FY23 delta cox5a, having a Ki of 1.94% (w/v). The retention of ethanol tolerance in the nuclear petites as compared to that of FY23 rho(0) is mirrored by the ethanol productivities of these nuclear mutants, being respectively 43% and 30% higher than that of the respiratory-sufficient parent strain. This demonstrates that, because of their respiratory deficiency, the nuclear petites are not subject to the Pasteur effect and so exhibit higher rates of fermentation.

Ethanol↗

Comparison of painful and painless left ventricular dysfunction recorded during ambulatory ventricular function monitoring in angina pectoris secondary to coronary artery disease.

Left ventricular (LV) function and the electrocardiogram of 55 patients with coronary artery disease and angina were monitored for a mean of 3.2 +/- 1.9 hours with an ambulatory LV function monitor. During the monitoring interval, patients performed daily activities such as sitting, walking, climbing stairs, and eating. Sixty episodes of transient reduction in ejection fraction of > 5% lasting > 60 seconds were observed in 24 patients; 13 episodes were associated with typical angina, but 47 were asymptomatic. Asymptomatic episodes had a shorter duration of ventricular dysfunction (116 +/- 49 vs 189 +/- 113 seconds; p < 0.05), and smaller increases in relative end-diastolic and end-systolic volumes (end-diastolic 0.9 +/- 5.4% vs 4.6 +/- 4.9% [p < 0.05], and end-systolic 21 +/- 11% vs 35 +/- 20% [p < 0.05]) than did symptomatic ones. When a subset of patients with both symptomatic and asymptomatic episodes were analyzed, similar results were observed: in asymptomatic episodes, duration was shorter (82 +/- 31 vs 200 +/- 110 seconds; p < 0.005), ejection fraction decrease was smaller (-7.3 +/- 2.6% vs -11.0 +/- 4.7%; p < 0.05), and end-systolic volume increase was smaller (23 +/- 12% vs 37 +/- 19%; p < 0.05). The data suggest that asymptomatic transient LV dysfunction is less severe and of shorter duration in patients with angina pectoris.

Angina Pectoris↗

Temporal relation between left ventricular dysfunction and chest pain in coronary artery disease during activities of daily living.

Forty-three ambulatory patients with angina of increasing frequency underwent continuous monitoring of left ventricular (LV) function for an average of 2.9 +/- 1.9 hours to determine the incidence and temporal sequence of LV dysfunction, ST-segment depression and chest pain. Indicators of ischemia were: a decrease in ejection fraction greater than 5% lasting greater than 1 minute; horizontal or downsloping ST-segment depression of greater than or equal to 1 mm; or onset of the patient's typical chest pain complex, or a combination of these. During the monitoring interval, subjects performed daily activities such as sitting, walking, climbing stairs and eating. In 11 patients, 22 episodes of chest pain or ST-segment depression, or both, were observed. Eighteen episodes were accompanied by a decrease in ejection fraction (9 patients); chest pain accompanied the decrease in ejection fraction during 13 episodes, whereas ST-segment changes occurred during 7. In 12 of 13 episodes the decrease in ejection fraction began earlier than the onset of chest pain, whereas in 1 patient ejection fraction decrease and chest pain onset started at the same time. The average interval from a decrease in ejection fraction to the onset of chest pain was 56 +/- 41 seconds (range 0 to 120). ST changes occurred after the onset of a decrease in ejection fraction in 6 of 7 episodes. The average interval from the onset of ejection fraction decrease and the onset of ST change was 99 +/- 91 seconds. These data suggest that LV dysfunction manifested by a decrease in ejection fraction is an earlier indicator of myocardial ischemia than is angina pectoris or electrocardiographic evidence of ischemia.

Activities of Daily Living↗

Role of protein kinase C in inhibition of renin release caused by vasoconstrictors.

It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release. By using these cultures, we found that ANG II (10(-7) M), AVP (10(-6) M), and NE (10(-5) M) inhibited renin release and increased the calcium permeability of the plasma membrane of the cultured cells. Both the effects on renin release and on calcium permeability could be diminished or even be abolished by the calcium channel blocker verapamil (Vp) (10(-5) M). ANG II, AVP, and NE led to an increased formation of diacylglycerol (DAG), a well-known stimulator of protein kinase C (PKC). Moreover, a direct stimulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-6) M) also inhibited renin release and increased the calcium permeability of the cell membrane. Similar to ANG II, AVP, and NE, the effects of TPA on calcium permeability and renin release could be diminished by Vp. In conclusion, these results point toward a common mechanism by which vasoconstrictors inhibit renin release from renal juxtaglomerular cells: ANG II, AVP, and NE activate a phospholipase C, which generates DAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Selection of microbial mutants tolerant to extreme environmental stress using continuous culture-control design.

The design of controllers for a continuous selection technique (BOICS; Brown and Oliver, 1982) is considered. This technique is used to obtain microbial mutants that are tolerant to extreme environmental stress. Applications of BOICS have been hampered by the problem of controller design. In this paper, a modified implementation of BOICS is considered which has a number of practical advantages. A model-based approach to controller design is taken. The case in which the stress is due to an inhibitory substance in the growth environment is considered. The analysis is intended to be applicable to any reasonable combination of organism and inhibitor. Conventional linear and time-invariant controllers are considered. Guidelines for the selection of controller parameters' values are suggested. The application of these guidelines requires that certain process parameters' values be identified. Methods by which these parameters' values can be identified are suggested. Simulation results indicate that the resulting controllers perform satisfactorily. This is confirmed by experimental data from a model selection experiment. A recipe for the design of controllers is a necessary part of a protocol for BOICS. It is hoped that the solution to the controller design problem that is offered in this paper will encourage further applications for the technique.

Bioreactors↗

Functional MRI of human olfaction.

PURPOSE: Our goal was to use functional MRI (fMRI) to measure brain activation in response to olfactory stimuli. METHOD: fMRI brain scans were obtained in 17 normal subjects (9 men, 8 women) using-multislice FLASH MRI in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. RESULTS: Activation was present in each section in all subjects. Subjective estimation of vapor intensity followed relative vapor pressure of stimuli presented (pyridine > amyl acetate > menthone) and were similar for both men and women. However, brain activation did not follow subjective responsiveness order but rather pyridine > menthone > amyl acetate, a pattern demonstrated by both men and women. Brain activation in women was consistently lower than in men for all vapors in all brain sections, although regions of activation did not differ. Activation occurred in regions previously recognized as associated with olfactory stimulation, including orbitofrontal and entorhinal cortex; however, extensive regions within frontal cortex including cingulate gyrus were also activated. Brain regions activated to odors considered pleasant or unpleasant did not differ. CONCLUSION: The techniques used in this study demonstrated that brain activation to olfactory stimuli could be measured quantitatively such that differences between groups of subjects (in this case men and women) could be compared. Although localization of brain activation was not the major thrust of this study, activation to olfactory stimuli was found not only in brain regions previously associated with processing of olfactory information but also in several other areas of frontal cortex, in cingulate gyrus, and in several components of the limbic system. This is the first study in which activation in human brain parenchyma of normal humans to olfactory stimuli has been quantitated by fMRI.

Adult↗

Mapping brain activation to odorants in patients with smell loss by functional MRI.

PURPOSE: Our goal was to use functional MRI (fMRI) to develop an objective, noninvasive technique by which patients with smell loss can be identified, their abnormalities quantitated, their results compared with findings in normal subjects, and visual representation of their CNS pathology obtained. METHOD: Functional MR brain scans were obtained in eight patients with hyposmia in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions using multislice FLASH MRI. Results were compared with similar studies performed in 17 normal subjects. Activation images were derived using correlation analysis, and ratios of area of brain activated to total brain area were obtained. RESULTS: Brain activation to each stimulus was lower in each section in patients compared with normal subjects and reached statistical significance for mean activation for each odor and in six of the nine individual sections studied. Activation in patients was found in regions previously associated with CNS processing of olfactory stimuli in normal subjects, but activation in patients was much less, particularly in inferior frontal and cingulate gyral regions of frontal cortex and in regions of medial and posterior temporal cortex. CONCLUSION: These results demonstrate quantitative CNS changes in smell function in response to olfactory stimuli in patients with hyposmia, demonstrate a novel, objective method by which these patients can be identified, and provide maps of the CNS changes associated with their smell loss.

Adult↗

Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI.

PURPOSE: Our goal was to demonstrate that medical therapy in patients with smell loss (hyposmia) that restored olfactory function toward or to normal could be verified and quantitated by functional MRI (fMRI) of brain and that visual representation of these changes could be used to identify these patients. METHOD: Multislice FLASH MR or echo planar MR brain scans were obtained in four patients with hyposmia in response to three olfactory stimuli both before and after treatment with theophylline. Activation images were derived using correlation analysis, and ratios of brain area activated to total brain area were obtained. RESULTS: Prior to treatment, all patients stated that they could not smell; these losses were confirmed by standard psychophysical tests. At this time, fMRI brain activation in response to odors was significantly less than that measured in normal volunteers and similar to activation measured previously in other patients with a similar type of hyposmia. After treatment, subjective smell function improved in three patients and no improvement occurred in one; results were confirmed by psychophysical tests. In each patient in whom smell acuity improved, brain activation in response to each odor increased in each section and mean activation increased significantly for each odor. Activation increased in all regions previously associated with olfactory stimulation and was particularly apparent in orbitofrontal cortex, frontal lobe component of cingulate gyri, temporal lobe gyri, and hippocampus. There also was consistent activation in superior, middle, and inferior frontal lobe gyri. There were no changes in brain activation after treatment in the patient in whom smell did not improve. CONCLUSION: These results demonstrate that theophylline is an effective therapeutic agent to correct hyposmia in some patients with smell loss. These changes have been documented by fMRI brain scans using olfactory stimuli. This is the first study in which this type of objective improvement following medical treatment has been demonstrated in patients with hyposmia.

Adult↗

Odor memory induces brain activation as measured by functional MRI.

PURPOSE: Our goal was to use functional MRI (fMRI) to measure brain activation in response to imagination of odors in humans. METHOD: fMR brain scans were obtained in 21 normal subjects (9 men, 12 women) using multislice FLASH MRI in response to imagination of odors of banana and peppermint and to the actual smells of the corresponding odors of amyl acetate and menthone, respectively, in three coronal sections selected from anterior to posterior temporal brain regions. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging, both before and after theophylline treatment, which returned smell function to or toward normal in each patient. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. RESULTS: Activation was present in each section in all normal subjects and in each patient after imagination of each vapor. In normal subjects, brain activation in response to imagination of odors was significantly less than that in response to the actual smell of these odors, and activation following imagination of banana odor was significantly greater in men than in women, as was previously reported for the actual smell of the odor of amyl acetate. However, in relative terms, albeit at an absolute lower brain activation level, the ratio of brain activation by imagination of banana to activation by actual amyl acetate odor was about twice as high in women as in men. Before treatment, in patients with hyposmia, brain activation in response to odor imagination was greater than after presentation of the actual odor itself. After treatment, in patients with hyposmia in whom smell acuity returned to or toward normal, brain activation in response to odor imagination was not significantly different quantitatively from that before treatment; however, brain activation in response to the actual odor was significantly greater than that in response to imagination of the corresponding odor. Brain regions activated by both odor imagination and actual corresponding odor were similar and consistent with regions previously described as responding to odors. CONCLUSION: These studies indicate that (a) odors can be imagined and similar brain regions are activated by both imagined and corresponding actual odors; (b) imagination of odors elicits quantitatively less brain activation than do actual smells of corresponding odors in normal subjects; (c) absolute brain activation in men by odor imagination is greater than in women for some odors, but on a relative basis, the ratio for odor imagination to actual smell in women is twice that in men; (d) odor imagination, once the odor has been experienced, is present, recallable, and capable of inducing a relatively constant degree of brain activation even in the absence of the ability to recognize an actual corresponding odor.

Adult↗