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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 91 records · Page 5Linked to original sources

Stability of gastrointestinal glutathione peroxidase mRNA in selenium deficiency depends on its 3'UTR.

Selenoproteins decrease upon selenium-deprivation according to their hierarchical ranking. Whereas classical glutathione peroxidase (cGPx) responds to decreased selenium supply with a complete loss of protein and a marked reduction of mRNA levels, gastrointestinal glutathione peroxidase (GI-GPx) remains detectable and its mRNA is stable. The impact of the 3'UTR on cGPx and GI-GPx mRNA stability was studied in stably transfected HepG2 cells with combinations of mutually exchanged coding regions and 3'UTRs of human cGPx and GI-GPx. Stability of chimeric mRNAs was measured by competitive RT-PCR. We found that GI-GPx 3'UTR is sufficient to stabilize its own mRNA but not that of cGPx.

3' Untranslated Regions↗

Functions of GI-GPx: lessons from selenium-dependent expression and intracellular localization.

Gastro intestinal glutathione peroxidase (GI-GPx) is one of the four distinct mammalian selenoperoxidases. It had been reported to be restricted to the gastrointestinal tract but has more recently been identified also in human liver and some tumor cell lines. GI-GPx ranks high in the hierarchy of selenoproteins. The GI-GPx mRNA rather increases than decreases in selenium deficiency. GI-GPx protein responds poorly to selenium deprivation and increases fast upon resupplementation. Putative biological roles of GI-GPx, e.g. protection against food-born hydroperoxides, redox-regulation of proliferation or apoptosis, and modulation of mucosal immunity, are discussed in the light of cellular and subcellular distribution, transcriptional regulation and observations with k.o. mice.

Animals↗

Metabolic engineering of the morphology of Aspergillus.

The morphology of filamentous organisms in submerged cultivation is a subject of considerable interest, notably due to the influence of morphology on process productivity. The relationship between process parameters and morphology is complex: the interactions between process variables, productivity, rheology, and macro- and micro-morphology create difficulties in defining and separating cause and effect. Additionally, organism physiology contributes a further level of complexity which means that the desired morphology (for optimum process performance and productivity) is likely to be process specific. However, a number of studies with increasingly powerful image analysis systems have yielded valuable information on what these desirable morphologies are likely to be. In parallel, studies on a variety of morphological mutants means that information on the genes involved in morphology is beginning to emerge. Indeed, we are now beginning to understand how morphology may be controlled at the molecular level. Coupling this knowledge with the tools of molecular biology means that it is now possible to design and engineer the morphology of organisms for specific bioprocesses. Tailor making strains with defined morphologies represents a clear advantage in optimization of submerged bioprocesses with filamentous organisms.

Aspergillus↗

The inverted repeats of IS1384, a newly described insertion sequence from Pseudomonas putida strain H, represent the specific target for integration of IS1383.

Analysis of a region on plasmid pPGH1 from Pseudomonas putida strain H that is flanked by two copies of IS1383 has revealed an additional element with the typical features of a bacterial insertion sequence. This new IS element, designated IS1384, contains a single ORF of 972 bp, and is flanked by 9-bp inverted repeats. Based on sequence homology and structural characteristics of the putative transposase it encodes, IS1384 belongs to the IS5 subgroup of the IS5 family. Two copies of IS1384 are present on plasmid pPGH1, whereas none could be detected on the chromosome of P. putida strain H. Sequence analysis revealed the presence of two truncated copies of IS1384 on the second plasmid in this strain, pPGH2. The inverted repeats of all IS1384 copies (including the truncated ones) are interrupted by the integration of an IS1383 element. All integrations were found to be site- and orientation-specific. PCR studies and sequence data indicate that IS1383 can form a circular intermediate on excision. In the circular form, the previously described 13-bp inverted repeats of IS1383 are separated by 10 bp that are identical to the 5-bp motif that flanks each side of the element when it is integrated in its target. We provide evidence that these additional nucleotides, although not of inverted symmetry, represent an essential part of the inverted repeats. Furthermore, the data indicate that IS1383 integrated into the inverted repeats of IS1384 by a site-specific recombination rather than a site-specific insertion event.

Base Sequence↗

The cyo operon of Pseudomonas putida is involved in carbon catabolite repression of phenol degradation.

A bicistronic reporter consisting of the promoterless genes aacC1 (conferring gentamycin resistance) and lacZ fused to the catabolic promoter of the phenol degradation genes was used to identify and analyse mutants of Pseudomonas putida with altered carbon catabolite repression (CR) of phenol degradation. Out of approximately 2500 mini-Tn5 mutants analysed so far, 12 mutants that were resistant to gentamycin during growth on succinate were identified. In eight of these mutants mini-Tn5 was inserted into one of the genes of the cyo operon. The cyo operon encodes the cytochrome o ubiquinol oxidase, the terminal oxidase of the cyanide-sensitive branch of the respiratory chain. In these mutants the activity of the PphlA promoter was significantly increased during growth on succinate and reached 15-20% of that found during growth with the non-repressing carbon source pyruvate. During growth on glucose the reduction of CR was less obvious, during growth on lactate CR was unchanged. The possible significance of the cyo operon for the generation of signal(s) for carbon catabolite repression is discussed.

Bacterial Proteins↗

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes.

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Adult↗

Interleukin-6 is a major effector molecule of short-term G-CSF treatment inducing bone metabolism and an acute-phase response.

OBJECTIVE: The biological steps leading to hematopoietic progenitor cell (HPC) mobilization from the bone marrow to the peripheral blood compartment during G-CSF treatment are still poorly defined. In this study, we investigated G-CSF-mediated secretion of cytokines as potential mediators. MATERIALS AND METHODS: Plasma and urine samples from G-CSF-mobilized donors for HPC transplantation were collected before and during mobilization therapy. Interleukin-6 (IL-6), alkaline phosphatase (ALP), bone-specific ALP (bone ALP), C-reactive protein (CRP), lipopolysaccharide binding protein (LPB), CD34+ cells and urinary deoxypyridinoline (DPD) concentrations were measured and statistically correlated. RESULTS: IL-6 was highly elevated at days 4 and 5 of G-CSF treatment. G-CSF administration led to elevation of IL-6 parallel to the appearance of CD34+ cells in the peripheral blood. Major metabolic changes such as high bone ALP plasma concentration and urinary excretion of deoxypyridinoline (DPD), indicating stimulation of bone metabolism, were observed. Elevated concentrations of CRP and LPB indicated an acute-phase response. Furthermore, CRP concentrations correlated significantly with the percentage of mobilized CD34+ cells. CONCLUSION: Based on these findings, we propose IL-6 as a major physiological effector molecule of G-CSF treatment that induces bone metabolism and an acute-phase reaction along with mobilization of CD34+ cells in the peripheral blood. IL-6 may be responsible for osteopenia observed during short- and long-term G-CSF treatment. These observations may also have implications for G-CSF treatment of patients with plasmocytoma.

Acute-Phase Reaction↗

Chromatin remodeling in development and differentiation.

During development and differentiation, early inductive processes that influence cell fate at a later stage leave marks at distinct gene loci that are maintained through several rounds of mitosis. The structure of chromatin is part of this epigenetic memory that restricts or permits differential expression of genes in descendant cells. Establishing a cell-type-specific chromatin pattern thus predestines future cell differentiation and deters cell-lineage infidelity, as it often occurs during neoplastic transformation. As such, understanding the dynamics and mechanisms underlying chromatin remodeling has been a major focus of recent molecular genetic research that holds great promise for biomedical discoveries.

Animals↗

Hemorheology and renal function during cardiopulmonary bypass in infants.

BACKGROUND: Acute renal failure is an occasional complication after cardiopulmonary bypass in infants. Whereas it is well known that postoperative hemodynamics inflict acute renal failure, the influence of extracorporeal circulation on the kidney is less clear. Moreover, changes in blood viscosity occur during and after surgery, which may influence renal dysfunction. For this reason, we investigated the impact of blood viscosity on renal function during cardiopulmonary bypass. METHODS: In 34 patients weighting less than 10 kg, we performed repeated analysis of urine, blood, and plasma viscosity. RESULTS: Polyuria and proteinuria that appeared during cardiopulmonary bypass indicated an elevated transglomerular filtration gradient, which recovered within 24 hours. The appearance of N-acetyl-beta-D-glucosaminidase in the urine, and elevated excretion of sodium, were additionally indicative of mild tubular damage. Elevation of blood viscosity during hypothermic perfusion showed a statistical correlation with proteinuria and N-acetyl-beta-D-glucosaminidaseuria. With hypothermia, the relation of blood viscosity to plasma viscosity became stronger, while the relation to the hematocrit decreased compared to normothermia. CONCLUSIONS: During cardiopulmonary bypass perfusion, the kidney can be stressed by proteinuria and mild tubular damage. Our data provide evidence that the kidneys can be protected by improved blood viscosity during cardioplegia, but this needs confirmation in a prospective interventional study.

Acetylglucosaminidase↗

Host finding and oviposition behavior in a chrysomelid specialist--the importance of host plant surface waxes.

Although several studies have elucidated the role of plant epicuticular waxes in host recognition and oviposition by herbivorous insects, there is little known about this subject in Chrysomelidae. In the present study, chemical cues for host recognition behavior and oviposition by the monophagous chrysomelid species Cassida stigmatica were investigated with special regard to surface waxes of the host plant. Tanacetum vulgare (Asteraceae). After hibernation in the soil, adults of this species must climb the plant's petioles, which emerge from the ground in spring. The response of adult C. stigmatica to contact and volatile cues from petioles and leaves of T. vulgare was investigated in a "stem arena," in which differently treated petioles and petiole dummies were offered. Volatile and contact cues of T. vulgare petioles served as well for host recognition. The contact cues were isolated from the petioles and leaves by hexane extraction and by cellulose acetate treatment, which removed cuticular waxes. The attractive volatiles were not extracted sufficiently by hexane. To examine the role of cuticular waxes of the host leaf surface in oviposition, female C. stigmatica were offered intact leaflets and leaflets from which cuticular waxes had been stripped by cellulose acetate treatment. Females did not discriminate between intact and stripped leaflets when only the upper leaf surfaces were offered. However. when the lower leaf surfaces that are generally used as oviposition sites were offered, C. stigmatica preferred to lay eggs on intact leaflets. We conclude that waxes of the lower leaf surface contain crucial information for oviposition in C. stigmatica.

Animals↗

Sequestration of host plant glucosinolates in the defensive hemolymph of the sawfly Athalia rosae.

Interactions between insects and glucosinolate-containing plant species have been investigated for a long time. Although the glucosinolate-myrosinase system is believed to act as a defense mechanism against generalist herbivores and fungi, several specialist insects use these secondary metabolites for host plant finding and acceptance and can handle them physiologically. However, sequestration of glucosinolates in specialist herbivores has been less well studied. Larvae of the tumip sawfly Athalia rosae feed on several glucosinolate-containing plant species. When larvae are disturbed by antagonists, they release one or more small droplets of hemolymph from their integument. This "reflex bleeding" is used as a defense mechanism. Specific glucosinolate analysis, by conversion to desulfoglucosinolates and analysis of these by high-performance liquid chromatography coupled to diode array UV spectroscopy and mass spectrometry, revealed that larvae incorporate and concentrate the plant's characteristic glucosinolates from their hosts. Extracts of larvae that were reared on Sinapis alba contained sinalbin, even when the larvae were first starved for 22 hr and, thus, had empty guts. Hemolymph was analyzed from larvae that were reared on either S. alba, Brassica nigra, or Barbarea stricta. Leaves were analyzed from the same plants the larvae had fed on. Sinalbin (from S. alba), sinigrin (B. nigra), or glucobarbarin and glucobrassicin (B. stricta) were present in leaves in concentrations less than 1 micromol/g fresh weight, while the same glucosinolates could be detected in the larvae's hemolymph in concentrations between 10 and 31 micromol/g fresh weight, except that glucobrassicin was present only as a trace. In larval feces, only trace amounts of glucosinolates (sinalbin and sinigrin) could be detected. The glucosinolates were likewise found in freshly emerged adults, showing that the sequestered phytochemicals were transferred through the pupal stage.

Adaptation, Physiological↗

Sleep disorders and depression in patients with Parkinson's disease.

OBJECTIVES: Sleep disorders and depression are frequent in patients with Parkinson's disease (PD). However, the exact prevalence and the causality are still unknown. PATIENTS AND METHODS: We interviewed 56 consecutive PD patients and 59 age-matched healthy controls concerning sleep disorders and depression. Sleep Disorders Questionnaire (SDQ) and Zung Depression Scale (ZDS) were used as standardized valid and reliable psychometric tests. RESULTS: Patients with PD had significantly higher values in the clinical-diagnostic scale narcolepsy (P=0.01), correlating with the L-dopa dose (P=0.007). Concerning sleep apnea (P=0.49), psychiatric sleep disorder (P=1.00) and periodic limb movement disorder (P=0.12), no significant difference could be identified. PD patients showed significantly higher depression scores than healthy control subjects (P=0.01), increasing with the duration of PD (P=0.04). CONCLUSION: The significant higher narcolepsy score in PD patients must be seen due to dopaminergic medication and PD-specific neurodegeneration and immobility rather than due to narcolepsy. This leads to the conclusion that extreme caution is advised when carrying out the SDQ and interpreting the results in various persons and patient groups with motor problems. The strong association of depression, disease severity and sleep disorders in PD patients underlines the importance of identifying and treating both conditions in these patients.

Aged↗

Reduction of oxidative stress and AT1 receptor expression by the selective oestrogen receptor modulator idoxifene.

1. The beneficial vasoprotective effects of oestrogens are hampered by their side effects on secondary sexual organs. Selective oestrogen receptor modulators (SERM) such as idoxifene may exert beneficial vascular effects without influencing cancerogenesis in breast or uterus. 2. In order to investigate vascular effects of selective oestrogen receptor modulators, we examined the impact of idoxifene on production of reactive oxygen species as well as AT1 receptor expression in vascular smooth muscle cells (VSMC). 3. Idoxifene caused a concentration- and time-dependent down-regulation of AT1 receptor mRNA expression, as assessed by Northern analysis. The maximal effect was reached with 10 micromol l(-1) idoxifene after a 4 h incubation period (33+/-7% of control levels). Western blots showed a similar down-regulation of AT1 receptor protein to 36+/-11% of control levels. 4. Confocal laserscanning microscopy using the redox sensitive marker 2',7'-dichlorofluorescein (DCF) and measurement of NAD(P)H oxidase activity in cell homogenates revealed that idoxifene effectively blunted the angiotensin II-induced production of reactive oxygen species. 5. In order to investigate the signal transduction involved in SERM-induced modulation of AT1 receptor expression, VSMC were preincubation with PD98059, genistein, wortmannin, or N(omega)-Nitro-L-arginine. The results suggested that idoxifene caused AT1 receptor down-regulation through nitric oxide-dependent pathways. 6. In conclusion, idoxifene reduces angiotensin II-evoked oxidative stress in VSMC. This could in part be explained by idoxifene-induced down-regulation of AT1 receptor expression. These results demonstrate that the selective oestrogen receptor modulator idoxifene may exert beneficial vascular effects which could be useful for therapeutic regimen in postmenopausal women at risk for cardiovascular diseases.

Angiotensin Receptor Antagonists↗

Gender differences in long-term survival of patients with colorectal cancer.

BACKGROUND: Significant differences exist in the immunological response to surgery. This raises the possibility that gender differences exist concerning the outcome after curative colorectal cancer resection. METHODS: To study this hypothesis, a database of patients with colorectal cancer was analysed prospectively. RESULTS: Some 894 patients were included, 500 (55.9 per cent) were men and 394 (44.1 per cent) were women. Median follow-up was 54.5 months for the entire group and 63.3 months for survivors. The mean(s.e.m.) patient age was 65.3(0.4) years (women 66.1(0.6), men 64.7(0.5) years; P < 0.05). Women lived significantly longer after cancer resection than men (57.8(1.5) versus 52.0(1.3) months; P < 0.05, log rank 0.009). Disease-free survival was significantly longer in women than in men (51.6(1.7) versus 46.0(1.4) months; P < 0.05). Subgroup analysis revealed significant gender differences in Union Internacional Contra la Cancrum (UICC) stages I (n = 195, log rank 0.01) and UICC IV (n = 38, log rank 0.021). Survival analysis after rectal cancer resection revealed significant advantages for women (log rank 0.02), while no gender differences were detected when comparing patients after resection for colonic cancer. Moreover, patients older than 50 years (n = 635) showed significant gender-related survival differences (log rank 0.015). CONCLUSION: Significant gender differences following curative rectal cancer resection were observed. In women disease-free and overall survival were significantly longer. Whether or not these gender differences are related to gender-specific immune functions or to other gender-related local or systemic factors remains to be determined.

Age Factors↗

[Word generation in bilinguals--fMRI study with implications for language and memory processes].

For over a century the cerebral representation of language functions is a matter of debate. In Neuroscience language is regarded as one of the most lateralized cognitive functions. Thus, while the language which is acquired first in most cases is processed by the left hemisphere some studies in brain damaged but also experimental investigations propose a pivotal role of the right hemisphere in second language processing. By the advent of modern neuroimaging it is now possible to study language lateralization and bilinguality also in healthy subjects. We studied first and second language abilities in a group of bilingual, healthy individuals by means of functional magnetic resonance imaging (fMRI) with a word-fluency paradigm. While we found a predominantly left prefrontal activity during both first and also second language processing an additional right prefrontal activation was registered during the use of second language. Our findings are discussed on the basis of an interaction between language and memory processes.

Adult↗

[Diagnosis of lung embolism and underlying venous thrombosis in multi-slice spiral CT].

AIM: To determine the value of multi-slice CT for the diagnosis of acute pulmonary embolism and an underlying venous thrombosis. METHODS: 70 patients with clinically suspected acute pulmonary embolism were examined. Using multi-slice CT a combined examination of the pulmonary arteries and the veins of the lower limb, pelvis and abdomen was performed. Only one single bolus of 150 ml iopromid 300 was injected into a cubital vein with a flow of 4 ml/s. First, the pulmonary arteries were scanned with a slice thickness of 2.5 mm and a pitch of 1.5. On arrival of the contrast medium at the popliteal veins, indicated by bolus trakking, the veins of the lower limbs up to the end of the inferior vena cava were imaged using a slice thickness of 3.75 mm and a pitch of 1.5. The results could be compared with a ventilation-perfusion scan in 48 cases, with a Doppler ultrasound examination in 46 cases, and with a venography in 10 cases. Furthermore, the image quality of all arterial and venous regions was subjectively assessed. RESULTS: In all patients who underwent multi-slice CT the pulmonary arteries as well as the veins of the lower half of the body could be recorded completely. Regarding the pulmonary arteries the image quality showed excellent results for the central and segmental arteries. The region up to the 3rd division in subsegmental branches could be sufficiently judged. More peripherally, a diagnostic assessment was not possible. The image quality of the veins was excellent in all sections, except the calf, where a reliable diagnosis could not be made. The comparison with the other techniques confirmed the superiority of multi-slice CT concerning the central and segmental pulmonary arteries and the veins from the popliteal vein to the inferior vena cava. In contrast, peripheral pulmonary emboli can be detected more certainly in ventilation/perfusion scans. The veins of the calf can be evaluated more reliably with venography. CONCLUSION: Multi-slice CT proved to be an outstanding tool in the diagnosis of acute pulmonary embolism. The clinically suspected disease and a causing venous thrombosis can be detected in a fast and reliable way. At present, multi-slice CT is not suitable for the recognition of peripheral emboli. However, expected technical developments hold promise for future improvements.

Adult↗

[The Straub-Rotarex thrombectomy system: initial experiences].

BACKGROUND: To evaluate the efficacy, safety and limitations of a new rotational thrombectomy device (Straub-Rotarex) in clinical practice. MATERIAL AND METHODS: The Straub-Rotarex catheter is a new, wire-guided rotational thrombectomy device for the treatment of acute and subacute occlusions of the femoro-popliteal arteries. Over a 6-month period, 28 patients (64% male, mean age 69 +/- 9.5, 51-91 years) with 31 legs, mean duration of occlusion 4.4 +/- 4 (0-20) weeks, mean occlusion length 22 +/- 11 (5-40) cm were treated with the device, 5 of them in a cross-over technique. Target lesions: Aortic-femoral bypass, common iliac artery, external iliac artery, common femoral artery: 1 each, superficial femoral artery: 23, popliteal artery: 17. Initial stage of claudication: IIa: 6%, IIb: 72%, III: 16%, IV: 6%. RESULTS: Primary success rate: 90% (ipsilateral: 100%, cross-over: 40%). Stage of claudication after intervention: I: 85%, IIa: 7%, III: 4%, IV 4%, one amputation. 3-months follow-up: stage I: 86% (n = 24), IIa: 14% (n = 4), one femoro-popliteal bypass. Restenosis rate 18%. 6-months follow-up: stage I: 56% (n = 9), IIa: 31% (n = 5), IIb: 13% (n = 2). Restenosis rate 56%. COMPLICATIONS: 32% (5 perforations, three cases of embolism after PTA, one wire-induced dissection, one retroperitoneal bleeding coming from the puncture site). CONCLUSIONS: The new device is a useful tool for the treatment of (sub)acute long-distance occlusions of the SFA and popliteal artery and in-stent restenosis as well in antegrade technique. Main complications are perforations. Cross-over interventions can only be done in special cases.

Aged↗