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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 73 records · Page 4Linked to original sources
PubMed2000

Biodegradation of cis-1,4-polyisoprene rubbers by distinct actinomycetes: microbial strategies and detailed surface analysis.

Several actinomycetes isolated from nature were able to use both natural rubber (NR) and synthetic cis-1,4-polyisoprene rubber (IR) as a sole source of carbon. According to their degradation behavior, they were divided into two groups. Representatives of the first group grew only in direct contact to the rubber substrate and led to considerable disintegration of the material during cultivation. The second group consisted of weaker rubber decomposers that did not grow adhesively, as indicated by the formation of clear zones (translucent halos) around bacterial colonies after cultivation on NR dispersed in mineral agar. Taxonomic analysis of four selected strains based on 16S rRNA similarity examinations revealed two Gordonia sp. strains, VH2 and Kb2, and one Mycobacterium fortuitum strain, NF4, belonging to the first group as well as one Micromonospora aurantiaca strain, W2b, belonging to the second group. Schiff's reagent staining tests performed for each of the strains indicated colonization of the rubber surface, formation of a bacterial biofilm, and occurrence of compounds containing aldehyde groups during cultivation with NR latex gloves. Detailed analysis by means of scanning electron microscopy yielded further evidence for the two different microbial strategies and clarified the colonization efficiency. Thereby, strains VH2, Kb2, and NF4 directly adhered to and merged into the rubber material, while strain W2b produced mycelial corridors, especially on the surface of IR. Fourier transform infrared spectroscopy comprising the attenuated total reflectance technique was applied on NR latex gloves overgrown by cells of the Gordonia strains, which were the strongest rubber decomposers. Spectra demonstrated the decrease in number of cis-1,4 double bonds, the formation of carbonyl groups, and the change of the overall chemical environment, indicating that an oxidative attack at the double bond is the first metabolic step of the biodegradation process.

Actinomycetales↗
PubMed1999

Frontiers in Ultrashort Pulse Generation: Pushing the Limits in Linear and Nonlinear Optics.

Optical pulses in the 5-femtosecond range are produced by a variety of methods. Although different in technical detail, each method relies on the same three key components: spectral broadening due to the nonlinear optical Kerr effect, dispersion control, and ultrabroadband amplification. The state of the art of ultrashort pulse generation is reviewed with a focus on direct laser oscillator schemes.

Journal Article↗
PubMed1999

Transcriptional analysis of the cyclophilin A gene (cypA) of Streptomyces chrysomallus.

Streptomyces chrysomallus produces a 17.5-kDa cyclophilin (CypA) as a major cytosolic protein. Northern blotting of total RNA from S. chrysomallus showed that cypA is transcribed as a monocistronic 500-nt transcript during the vegetative growth phase only. Consistently, Western blot analysis and enzyme activity determinations revealed a high level of CypA which declined drastically when cultures entered postexponential phase. Primer extension experiments revealed that cypA is transcribed as a leaderless transcript with the startpoint of transcription and translation being the same AUG codon. Analysis of -10 and -35 regions revealed an EohrdB-specific promoter consensus sequence in accordance with the observed transcription during vegetative growth of cultures. The leaderless cypA mRNA sequence between codons 5 to 12 shows complementarity to an internal antidownstream box of 16S rRNA of Streptomyces lividans. This may indicate a possible interaction of the leaderless cypA transcript with the 16S mRNA in translation initiation.

Base Sequence↗
PubMed1999

[The diabetic foot: a look to the future].

The diabetic foot is still a medical problem of first order, not only for the quality of life of the affected patients but also for the society due to its high costs. Preventive measures are known to lower the risk for amputations by 40-85%. The introduction of interdisciplinary teams caring for diabetic patients with foot problems has been shown to reduce the incidence of amputations, and practicing physician should examine regularly the feet of diabetic patients. It is postulated that centres with interdisciplinary foot care teams should be established in the whole country to which patients with diabetic foot problems can be referred in order to diminish the rate of amputations.

Diabetic Foot↗
PubMed1999

Molecular characterization of the genes of actinomycin synthetase I and of a 4-methyl-3-hydroxyanthranilic acid carrier protein involved in the assembly of the acylpeptide chain of actinomycin in Streptomyces.

Actinomycin synthetase I (ACMS I) activates 4-methyl-3-hydroxyanthranilic acid, the precursor of the chromophoric moiety of the actinomycin, as adenylate. The gene acmA of ACMS I was identified upstream of the genes acmB and acmC encoding the two peptide synthetases ACMS II and ACMS III, respectively, which assemble the pentapeptide lactone rings of the antibiotic. Sequence analysis and expression of acmA in Streptomyces lividans as enzymatically active hexa-His-fusion confirmed the acmA gene product to be ACMS I. An open reading frame of 234 base pairs (acmD), which encodes a 78-amino acid protein with similarity to various acyl carrier proteins, is located downstream of acmA. The acmD gene was expressed in Escherichia coli as hexa-His-fusion protein (Acm acyl carrier protein (AcmACP)). ACMS I in the presence of ATP acylated the purified AcmACP with radioactive p-toluic acid, used as substrate in place of 4-MHA. Only 10% of the AcmACP from E. coli was acylated, suggesting insufficient modification with 4'-phosphopantetheine cofactor. Incubation of this AcmACP with a holo-ACP synthase and coenzyme A quantitatively established the holo-form of AcmACP. Enzyme assays in the presence of ACMS II showed that toluyl-AcmACP directly acylated the thioester-bound threonine on ACMS II. Thus, AcmACP is a 4-MHA carrier protein in the peptide chain initiation of actinomycin synthesis.

Amino Acid Sequence↗
PubMed1999

Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.

A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway.

Alkyl and Aryl Transferases↗
PubMed1999

Retrobulbar and peripheral capillary blood flow in hypercholesterolemic subjects.

PURPOSE: To assess retrobulbar blood flow velocities and finger nailfold capillary blood flow velocities (two readily accessible vascular beds) in subjects with primary hypercholesterolemia before and during lipid-lowering therapy. METHODS: Retrobulbar blood flow velocities and finger nailfold capillary blood flow velocities were assessed in 15 hypercholesterolemic subjects and in 15 age-matched and sex-matched healthy control subjects. In addition, the change in blood flow velocities after a 3-month period of lipid-lowering therapy was evaluated. RESULTS: No alterations in retrobulbar blood flow velocities after lipid-lowering therapy could be observed in hypercholesterolemic patients. Nailfold capillary blood flow velocity was slower in hypercholesterolemic subjects than control subjects immediately after local cooling (P = .0052), but this vascular dysregulation did not improve after lipid-lowering therapy (P = .58). CONCLUSIONS: Blood flow alterations, potentially caused by perturbed vascular endothelial function, may occur in nailfold capillaries of hypercholesterolemic subjects. Such alterations were not seen in retrobulbar vessels, and blood flow measures did not change during lipid-lowering therapy.

Blood Flow Velocity↗
PubMed1999

Effects of hypoosmolality on whole-body lipolysis in man.

Changes in extracellular osmolality, and thus in the cellular hydration state, appear to directly influence cell metabolism. The metabolic changes associated with cell swelling are inhibition of glycogenolysis, glycolysis, and proteolysis. Recent studies in our laboratory demonstrated diminished whole-body protein breakdown in humans during an acute hypoosmolar state. Because of the close interrelationship between carbohydrate and fat metabolism, we speculated that adipose tissue lipolysis and fatty acid oxidation are regulated by changes in extracellular osmolality. Therefore, we investigated the effect of artificially induced hypoosmolality on whole-body lipolysis and fat oxidation in seven healthy young men. Hypoosmolality was induced by intravenous administration of desmopressin, liberal ingestion of water, and infusion of hypotonic (0.45%) saline solution. Lipolysis was assessed by a stable-isotope method (2-[13C]-glycerol infusion). The glycerol rate of appearance (Ra), reflecting whole-body lipolysis, was higher under hypoosmolar compared with isoosmolar conditions (2.35+/-0.40 v 1.68+/-0.21 micromol/kg/min, P=.03). This was even more pronounced when lipolysis was suppressed during hyperinsulinemia and euglycemic clamping (0.90+/-0.08 v 0.61+/-0.03 micromol/kg/min, P=.002). However, plasma free fatty acid (FFA), glycerol, ketone body, insulin, and glucagon concentrations and carbohydrate and lipid oxidation measured by indirect calorimetry were not significantly altered by hypoosmolality. Plasma norepinephrine concentrations were lower under hypoosmolar conditions (P<.01 v control). In conclusion, hypoosmolality in vivo results in increased whole-body lipolysis, which is not due to changes in major lipolysis regulating hormones.

Adult↗
PubMed1999

Accelerated post-glucose glycaemia and altered alliesthesia-test in Seasonal Affective Disorder.

BACKGROUND: Little is known about the link between mood, food and metabolic function in Seasonal Affective Disorder (SAD). METHODS: We investigated this link in a combined glucose tolerance-alliesthesia test in eight SAD patients in winter before and after one week light therapy, and in summer. RESULTS: SAD patients exhibited faster post-glucose glycaemic and insulin responses (p <0.05), and increased hedonic ratings of high concentrated sucrose solutions (p <0.035) when depressed in winter than when euthymic (one week after light treatment or in summer). CONCLUSIONS: The rapid glycaemic and insulin responses to an oral glucose load may be a result of accelerated gastric emptying. LIMITATIONS: The number of studied patients was rather small and no control group was studied in parallel. CLINICAL RELEVANCE: the more rapid post-glucose glycaemia may impair glucose homeostasis in depressed SAD patients.

Adolescent↗
PubMed1999

[Polycystic ovary syndrome--only relevant in reproductive medicine?].

The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.

Diagnosis, Differential↗
PubMed1999

Clinical aspects of alveolar rhabdomyosarcoma with translocation t(1;13)(p36;q14) and hypotetraploidy.

Although most cases of alveolar rhabdomyosarcoma (RMS) are characterized by the chromosomal translocation t(2;13)(q35;q14), several cases have been reported with a variant t(1;13)(p36;q14). We present the clinical, morphological and cytogenetic features of an alveolar RMS in a 4-year-old boy. Chromosomal analysis revealed a hypertriploid to hypotetraploid karyotype with a t(1;13)(p36;q14) in all tumor cells. It appears that alveolar RMS with t(1;13) occurs in younger children and displays a higher incidence to upper and lower extremity than tumors with t(2;13).

Aneuploidy↗
PubMed1999

Effects of hyper- and hypoosmolality on whole body protein and glucose kinetics in humans.

To investigate the effect of acute changes of extracellular osmolality on whole body protein and glucose metabolism, we studied 10 male subjects during three conditions: hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl [2-5%; (wt/vol)] during 17 h; hypoosmolality was produced by intravenous administration of desmopressin, liberal water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolality study consisted of ad libitum oral water intake by the subjects. Leucine flux ([1-13C]leucine infusion technique), a parameter of whole body protein breakdown, decreased during the hypoosmolality study (P < 0. 02 vs. isoosmolality). The leucine oxidation rate decreased during the hypoosmolality study (P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose during hyperinsulinemic-euglycemic clamping increased less during the hypoosmolality study than during the isoosmolality study (P < 0.04). Plasma insulin decreased, and plasma nonesterified fatty acids, glycerol, and ketone body concentrations and lipid oxidation increased during the hypoosmolality study. It is concluded that acute alterations of plasma osmolality influence whole body protein, glucose, and lipid metabolism; hypoosmolality results in protein sparing associated with increased lipolysis and lipid oxidation and impaired insulin sensitivity.

Adult↗
PubMed1999

Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man.

Chronic glucocorticoid therapy results in negative bone and connective tissue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recombinant human GH (0.3 IU/kg per day s.c.), or a combination of GH (0.3 IU/kg per day s.c.) and IGF-I (80 microgram/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0.5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32.9+/-2.1 to 9.0+/-1.4 microgram/l (P<0.0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0.005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0.05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP concentrations (P<0.005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0.05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0.05 or less). These findings demonstrate that only the combination of GH and IGF-I, but not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.

Alkaline Phosphatase↗
PubMed1998

Arousal responses to inspiratory resistive loading during REM and non-REM sleep in normal men after short-term fragmentation/deprivation.

The arousal response to inspiratory resistive loading in normal men is known to be high during REM sleep compared to non-REM sleep. We investigated whether we could observe the same pattern, i.e. brisk arousal from REM sleep compared to non-REM sleep, in normal subjects who had undergone short-term sleep fragmentation/deprivation prior to the investigation. The arousal response to the repeated application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in 10 healthy men after a single night with 4 hours of acoustically fragmented sleep. The percentage of arousals to non-arousals occurring within 2 minutes of the load application was significantly higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4 and decreased significantly from stage REM to stage 2 and from stage 2 to stage 3/4. The mean time to arousal in REM was significantly shorter than in non-REM stage 3/4. The duration of sleep (comparing the results of the first with the second half of the sleep period time) did not modify the arousal response in stages 2 and 3/4. Despite short-term sleep fragmentation/deprivation the night before the study, the arousal response to external inspiratory resistive loading was brisker during REM than non-REM sleep in the healthy subjects studied. The responses were of the same magnitude as those induced in prior studies without pretest sleep disturbance. This is different from what is seen in patients with sleep apnea, where breathing disorders are worst during REM sleep and sleep fragmentation/deprivation leads to rapid deterioration of arousal responses to the spontaneously occurring airway occlusions.

Acoustic Stimulation↗
PubMed1998

[Lipid lowering therapy: new pathophysiologic aspects and clinical implications].

Lipid-lowering therapy reduces cardiovascular morbidity and mortality. Although atherosclerotic plaques regress under lipid-lowering therapy, only minor changes in arteriosclerotic plaques are angiographically detectable. These changes cannot fully explain all the benefits of lipid-lowering therapy. Additional factors independent of macroscopically detectable alterations in plaque size may contribute to the clinical effects of lipid-lowering therapy. Qualitative changes in the composition of atherosclerotic plaques may reduce the risk of subsequent plaque rupture. Furthermore, hypercholesterolemia is associated with endothelial dysfunction, i.e., impaired endothelium-mediated vasodilation, induction of adhesion molecules, and altered expression of growth factors. Lipid lowering seems to reverse endothelial dysfunction. Also, lipid-lowering therapy may reduce peripheral arterial resistance and hyperinsulinemia, and may improve erythrocyte deformability. These effects of lipid-lowering therapy may contribute to the clinical benefits. In particular, the concept of endothelial dysfunction as a first, reversible manifestation of target organ damage deserves further attention in the diagnosis and therapy of cardiovascular disease.

Arteriosclerosis↗
PubMed1998

Phosphinothricin-tripeptide synthetases from Streptomyces viridochromogenes.

Phosphinothricyl-alanyl-alanine (Pt tripeptide (Ptt), bialaphos) is a metabolite produced by Streptomyces viridochromogenes and Streptomyces hygroscopicus. It contains the unique phosphinoamino acid phosphinothricin (Pt), which after cleavage from Ptt is active as an inhibitor of glutamine synthetase. We have isolated three enzymes that assemble the building block of the Ptt peptide backbone in a nonribosomal mechanism. The first enzyme, named Ptt-synthetase I (PTTS I), activates N-acetyldemethylphosphinothricin (AcDMPt) as adenylate and thioester. Pt is not activated. PTTS I can also activate N-acetylphosphinothricin (AcPt) or N-acetylglutamate as structural analogues of AcDMPT. Native PTTS I has an estimated size of 62 kDa whereas the denatured form displays a size of 76 kDa. Immunoblot analysis and determination of its N-terminal protein sequence revealed that PTTS I is identical with the gene product of phsA. The phsA gene was previously identified near the Pt-resistance gene pat in the Ptt biosynthesis gene cluster in S. viridochromogenes. Besides PTTS I, two alanine-activating enzymes (PTTS II/III) were partially purified from S. viridochromogenes with estimated native sizes of ca. 120 kDa (enzyme 1) and ca. 140 kDa (enzyme 2). Both enzymes bind alanine as a thioester via the corresponding adenylate. Level of PTTS II/III and product formation were correlated with each other in several different strains of S. viridochromogenes. These results indicate that Ptt is synthesized by three peptide synthetases, each activating one single amino acid. The data also confirm previous genetic data, which suggest that AcDMPt-Ala-Ala is the precursor of Ptt.

Alanine↗