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Biomedical subjects

K Ahrens

Publications and source records attributed to K Ahrens.

At least 19 recordsLinked to original sources

Neuromuscular block and relative concentrations of mivacurium isomers under isoflurane versus propofol anaesthesia.

BACKGROUND AND OBJECTIVE: The augmentation of the effect of neuromuscular blocking drugs with volatile anaesthetics is well documented, but the mechanism remains unclear. The pharmacological interaction and relative plasma concentrations of mivacurium isomers were investigated during either propofol- or isoflurane-maintained anaesthesia. METHODS: Forty-four patients were randomly assigned to one of two groups: isoflurane or propofol. All patients received an initial dose of mivacurium 0.1 mg kg(-1). After recovery of the first twitch (T1) response measured by acceleromyography to 5%, a T1 depression of 90-99% was maintained by infusion. After a steady state was reached, blood samples were taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for T1 to 251/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index (time TW25-75) were recorded after stop of infusion. RESULTS: In the isoflurane group, lower infusion rates were needed (3.0 +/- 1.6 versus 3.6 +/- 1.6 microg kg(-1) min(-1)) and there was a slower recovery (significant for train-of-four ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its trans-trans isomer (in percentage of the total) were significantly higher in the isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%). CONCLUSIONS: For mivacurium, the phenomenon of 'potentiation' of the effect of muscle relaxants by volatile anaesthetics could be due to an increase in the plasma concentration of the potent trans-trans isomer.

Adult↗

Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial muscle precursors.

We cloned two isoforms of the Xenopus Eya1 orthologue. They show identical patterns of expression that closely resemble the previously described expression of XSix1, but partly differ from the expression of Eya1 in other vertebrates. XEya1 is expressed in the somites and hypaxial muscle precursors, but not in the pronephros. Moreover, all ectodermal placodes except the lens placode strongly express XEya1. At neural plate stages, ectodermal XEya1 expression starts in two domains, the anterior neural folds and a domain lateral to the neural folds. At tailbud stages, XEya1 expression continues in the adenohypophysis, all neurogenic placodes and placodally-derived structures including cranial ganglia, the otic vesicle and lateral line primordia.

Amino Acid Sequence↗

Regulation of carbon and electron flow in Clostridium butyricum VPI 3266 grown on glucose-glycerol mixtures.

The metabolism of Clostridium butyricum was manipulated at pH 6.5 and in phosphate-limited chemostat culture by changing the overall degree of reduction of the substrate using mixtures of glucose and glycerol. Cultures grown on glucose alone produced only acids (acetate, butyrate, and lactate) and a high level of hydrogen. In contrast, when glycerol was metabolized, 1,3-propanediol became the major product, the specific rate of acid formation decreased, and a low level of hydrogen was observed. Glycerol consumption was associated with the induction of (i) a glycerol dehydrogenase and a dihydroxyacetone kinase feeding glycerol into the central metabolism and (ii) an oxygen-sensitive glycerol dehydratase and an NAD-dependent 1,3-propanediol dehydrogenase involved in propanediol formation. The redirection of the electron flow from hydrogen to NADH formation was associated with a sharp decrease in the in vitro hydrogenase activity and the acetyl coenzyme A (CoA)/free CoA ratio that allows the NADH-ferredoxin oxidoreductase bidirectional enzyme to operate so as to reduce NAD in this culture. The decrease in acetate and butyrate formation was not explained by changes in the concentration of phosphotransacylases and acetate and butyrate kinases but by changes in in vivo substrate concentrations, as reflected by the sharp decrease in the acetyl-CoA/free CoA and butyryl-CoA/free CoA ratios and the sharp increase in the ATP/ADP ratio in the culture grown with glucose and glycerol compared with that in the culture grown with glucose alone. As previously reported for Clostridium acetobutylicum (L. Girbal, I. Vasconcelos, and P. Soucaille, J. Bacteriol. 176:6146-6147, 1994), the transmembrane pH of C. butyricum is inverted (more acidic inside) when the in vivo activity of hydrogenase is decreased (cultures grown on glucose-glycerol mixture). For both cultures, the stoichiometry of the H(+) ATPase was shown to remain constant and equal to 3 protons exported per molecule of ATP consumed.

Carbon↗

Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia.

Overexpression and/or mutations of oncogenes, tumour suppressor genes and tumour rejection genes have been observed in several human malignancies. Their analyses might be of diagnostic importance. Therefore, malignant hepatocytes derived from hepatocellular carcinoma (HCC) tissue as well as non-malignant hepatocytes derived from focal nodular hyperplasia (FNH) were studied. Samples containing normal human hepatocytes (HC) served as controls. Cellular material was obtained by fine-needle aspiration biopsy guided by ultrasound. Cells were analysed for expression and mutation of the oncogene MDM2, the genes GAGE-1, -2 coding for tumour-associated antigens and the candidate tumour suppressor gene FHIT. Different patterns of non-mutant FHIT transcripts including precise deletion of exons were found in 7/10 HCC, 2/10 FNH and 2/10 HC. However, expression of non-mutant GAGE-1, -2 RNA was demonstrated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples). Neither GAGE-1, -2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1, -2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1, -2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms.

Acid Anhydride Hydrolases↗

Kinetic, dynamic, and pathway studies of glycerol metabolism by Klebsiella pneumoniae in anaerobic continuous culture: IV. Enzymes and fluxes of pyruvate metabolism.

The activities of pyruvate kinase (PK), pyruvate: formate-lyase (PFL), pyruvate dehydrogenase (PDH), and citrate synthase (CS) involved in the anaerobic glycerol conversion by Klebsiella pneumoniae were studied in continuous culture under conditions of steady states and sustained oscillations. Both the in vitro and in vivo activities of PK, PFL, and PDH are strongly affected by the substrate concentration and its uptake rate, as is the in vitro activity of CS. The flux from phosphoenolpyruvate to pyruvate is found to be mainly regulated on a genetic level by the synthesis rate of PK, particularly at low substrate concentration and low growth rate. In contrast, the conversion of pyruvate to acetyl-CoA is mainly regulated on a metabolic level by the in vivo activities of PFL and PDH. The ratio of in vitro to in vivo activities is in the range of 1 to 1.5 for PK, 5 to 17 for PFL and 5 to 80 for PDH under the experimental conditions. The regulation of in vivo activity and synthesis of these enzymes is sensitive to fluctuations of culture conditions, leading to oscillations of both the in vitro and in vivo activities. In particular, PFL is strongly affected during oscillations; its average in vitro activity is only about half of its corresponding steady-state value under similar environmental conditions. The average in vitro activities of PDH and PK under oscillations are close to their corresponding steady-state values. In contrast to all other enzymes measured for the glycerol metabolism by K. pneumoniae PFL and PDH are more effectively in vivo utilized under oscillations than under steady state, underlining the peculiar role of pyruvate metabolism in the dynamic responses of the culture.

Acetyltransferases↗

Kinetic, dynamic, and pathway studies of glycerol metabolism by Klebsiella pneumoniae in anaerobic continuous culture: III. Enzymes and fluxes of glycerol dissimilation and 1,3-propanediol formation.

The initial steps of glycerol dissimilation and 1,3-propanediol (1, 3-PD) formation by Klebsiella pneumoniae anaerobically grown on glycerol were studied by quantifying the in vitro and in vivo activities of enzymes in continuous culture under conditions of steady state and oscillation and during transient phases. The enzymes studied included glycerol dehydrogenase (GDH), glycerol dehydratase (GDHt), and 1,3-propanediol oxidoreductase (PDOR). Three conclusions can be drawn from the steady-state results. First, glycerol concentration in the culture is a key parameter that inversely affects the in vitro activities (concentrations) of all three enzymes, but has a positive effect on their in vivo activities. Growth rate significantly affects the ratio of in vitro and in vivo enzyme activities under low glycerol concentrations, but not under glycerol excess. Second, whereas the flux through the oxidative pathway of glycerol dissimilation is governed mainly by the regulation of in vivo enzyme activity on a metabolic level, the flux through the reductive pathway is largely controlled by the synthesis of enzymes. Third, GDHt is a major rate-liming enzyme for the consumption of glycerol and the formation of 1,3-PD in K. pneumoniae at high glycerol concentrations. Results from oscillating cultures revealed that both in vitro and in vivo activities of the enzymes oscillated. The average values of the in vitro activities during an oscillation cycle agreed well with their corresponding values for nonoscillating cultures under similar environmental conditions. Experiments with step changes in the feed concentration of glycerol demonstrated that growth and product formation are very sensitive to changes of substrate concentration in the culture. This sensitivity is due to the dynamic responses of the genetic and metabolic networks. They should be considered when modeling the dynamics of the culture and attempting to improve the formation of 1,3-PD.

Alcohol Oxidoreductases↗

CIF150, a human cofactor for transcription factor IID-dependent initiator function.

The transcription factor IID (TFIID) complex is highly conserved between the Drosophila and mammalian systems. A mammalian homolog has been described for all the Drosophila TATA box-binding protein-associated factors (TAFs), with the exception of dTAF(II)150. We previously reported the identification of CIF, an essential cofactor for TFIID-dependent transcription from promoters containing initiator (Inr) elements. Here we describe the molecular cloning of CIF150, the human homolog of dTAF(II)150, and present biochemical evidence that this factor is involved in Inr activity. CIF150 is capable of mediating TFIID-dependent Inr activity in a complementation assay, and a protein fraction lacking Inr activity lacks detectable amounts of CIF150. Despite the striking similarity to dTAF(II)150, CIF150 does not appear to be associated with human TFIID. However, in vitro binding assays revealed a specific and direct interaction between CIF150 and hTAF(II)135. This interaction might be structurally important for the functional interaction between CIF150 and human TFIID, since CIF150 stabilizes TFIID binding to a core promoter.

Amino Acid Sequence↗

The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several U5-specific proteins, including an RNA unwindase, a homologue of ribosomal elongation factor EF-2, and a novel WD-40 protein.

The human small nuclear ribonucleoprotein (snRNP) U5 is biochemically the most complex of the snRNP particles, containing not only the Sm core proteins but also 10 particle-specific proteins. Several of these proteins have sequence motifs which suggest that they participate in conformational changes of RNA and protein. Together, the specific proteins comprise 85% of the mass of the U5 snRNP particle. Therefore, protein-protein interactions should be highly important for both the architecture and the function of this particle. We investigated protein-protein interactions using both native and recombinant U5-specific proteins. Native U5 proteins were obtained by dissociation of U5 snRNP particles with the chaotropic salt sodium thiocyanate. A stable, RNA-free complex containing the 116-kDa EF-2 homologue (116kD), the 200kD RNA unwindase, the 220kD protein, which is the orthologue of the yeast Prp8p protein, and the U5-40kD protein was detected by sedimentation analysis of the dissociated proteins. By cDNA cloning, we show that the 40kD protein is a novel WD-40 repeat protein and is thus likely to mediate regulated protein-protein interactions. Additional biochemical analyses demonstrated that the 220kD protein binds simultaneously to the 40- and the 116kD proteins and probably also to the 200kD protein. Since the 220kD protein is also known to contact both the pre-mRNA and the U5 snRNA, it is in a position to relay the functional state of the spliceosome to the other proteins in the complex and thus modulate their activity.

Amino Acid Sequence↗

Participant roles and the processing of verbs during sentence comprehension.

This paper explores the nature of thematic information made available when a verb is accessed during sentence comprehension. Following Shapiro, Zurif, and Grimshaw (1987), a cross-modal lexical decision (interference) task was employed to examine whether either the number of argument structures or the number of participant (thematic) roles inherent in a verb cause an increase in processing load upon access of the verb. It was determined that there was no evidence for such an increased processing load covarying with the number of argument structures of the verb, at least for those verb types examined in this study. However, there was an increase in processing load as a direct function of the number of participant roles carried by the verb. It is concluded that the participant roles (thematic roles associated with the central meaning of the verb) are stored with the representation of a verb and are made immediately available upon access of the verb for further processing during comprehension.

Female↗

A TnphoA insertion within the Bradyrhizobium japonicum sipS gene, homologous to prokaryotic signal peptidases, results in extensive changes in the expression of PBM-specific nodulins of infected soybean (Glycine max) cells.

Bradyrhizobium japonicum mutant 132 was obtained by random TnphoA mutagenesis of strain 110spc4. A 6.5 kb BamHI kanamycin-resistance-coding DNA fragment of mutant 132 was used as a hybridization probe to clone the corresponding wild-type fragment. DNA sequence analysis of a 3213 bp BamHI-ClaI fragment revealed that three open reading frames (ORFs) were encoded in the same orientation. Based on sequence similarities to other proteins in the database, the second ORF was called sipS (signal peptidase). The TnphoA insertion in mutant 132 was found to be in frame near the 3' end of sipS. The resulting SipS-PhoA hybrid polypeptide was shown to be expressed in free-living B. japonicum and in Escherichia coli cultures. An immunoblot analysis with a polyclonal antibody directed against the alkaline phosphatase revealed the appearance of a weak signal of a 70 kDa polypeptide both in B. japonicum and in E. coli, in agreement with the calculated size of the hybrid polypeptide. A much stronger 52 kDa band was also detected. Mutant 132 was specifically disturbed in the interaction with soybean (Glycine max) when the bacteria were released from the infection threads. The bacteroids were not stably maintained within the symbiosome. Numerous vesicles were found in the plant cytosol, which finally resulted in the formation of large vacuoles within the infected nodule cells. Immunohistochemical analyses with antibodies directed against nodulins of the peribacteroid membrane indicated a lower expression of these proteins. The mutant phenotype was genetically complemented by a 4.4 kb BamHI fragment including sipS. Subfragments thereof also complemented a temperature-sensitive E. coli lepB mutant, demonstrating that the B. japonicum fragment was functionally replacing Lepts in E. coli. Genetic studies suggested that the three genes are organized in one common operon which is expressed from a promoter upstream of the sequenced region. Inactivation of the gene downstream of sipS did not result in a detectable phenotype.

Alkaline Phosphatase↗

[Disability payments in diabetes mellitus in social security: what is necessary?].

Since their publication in 1974 the recommendations of the "German Society for Public and Private Welfare" are regarded as competent guideline for the allocation of grants concerning the diet for diabetic subjects according to section 23 part 4, position 2 BSHG (Federal German Law for Social Security). The former nutrition concepts are compared to the current international conceptions regarding the diet of diabetic individuals. Possible variations concerning food plans are shown in model plans considering realistic habits of consumption. Our analysis justifies additional expenses limited to about 20 to 30% for insulin-dependent diabetic subjects compared to an isocaloric regular diet. Additional expenses for obese non-insulin-dependent diabetic subjects are not necessary. There is an extremely slim portion allocated for food within the social security benefit according to section 22 BSHG. That will require an comprehensive supply of education for the realisation of the current recommendations for nutrition. The education programmes for compiling suitable food plans to remain within the scheduled cost limits need to be organized by regional carriers of social welfare, whereby public Health offices could make an important contribution.

Costs and Cost Analysis↗

[Delayed absorption of carbohydrates in the therapy of Type II diabetes: comparison between dietary (Muesli) and pharmacological (Alpha-glucosidase inhibition) modification].

Slowly resorbable carbohydrates are preferred in the dietetic therapy of patients with type 2 diabetes. In this study we compared the efficacy of a "müsli" with the alpha-glucosidase inhibitor miglitol in delaying the resorption of carbohydrates. 24 patients with NIDDM took, in randomized order, four different breakfasts with equal amounts of carbohydrate: a standard breakfast with bread and marmelade, a müsli, and both breakfasts with 100 mg miglitol. We calculated the maximal blood glucose concentration, the postprandial difference, the time of the maximum and the area under the curve (AUC). The postprandial blood glucose increase after the müsli breakfast was significantly lower compared with the standard breakfast (maximal blood glucose 12.3 vs. 13.9 mmol/l, postprandial difference 3.6 vs. 5.1 mml/l, AUC 360 vs, 468 mmol/l x min). The blood glucose increase after the standard breakfast with miglitol was even lower (maximum 11.6 mmol/l, postprandial difference 2.9 mmol/l, AUC 241 mmol/l x min). Miglitol also lowered the blood glucose values after the müsli breakfast. This study shows that the alpha-glucosidase inhibitor miglitol in a dose of 100 mg is more effective in lowering the postprandial blood glucose increase than a müsli. In cases of non-acceptance of a modern diet with slowly resorbable carbohydrates, alpha-glucosidase inhibitors may be a therapeutic alternative.

1-Deoxynojirimycin↗

Physical factors influencing the blood glucose response to different breads in type II diabetic patients.

Blood glucose responses to test meals containing 75 g of different breads were compared in 103 type II diabetic patients under sulfonyl urea treatment. Nine breads differing in type of cereal, physical structure, and dietary fiber content were studied using pairwise intraindividual comparisons. It could be shown that the type of cereal and the fiber content had no significant influence upon the maximal or mean postprandial blood glucose increase. Coarse-grained breads, however, resulted in significantly lower blood glucose responses than breads that were finer grained or were produced from flour. Physical properties determining the access of intestinal hydrolytic enzymes to ingested carbohydrates seem to be major factors that influence postprandial blood glucose responses.

Adult↗

Smoking intervention: combination therapy using nicotine chewing gum and the American Lung Association's "Freedom from Smoking" manuals.

The smoking cessation efficacy of a two-session group program using the American Lung Association's "Freedom from Smoking" self-help manuals, nicotine gum, and brief, repeated professional supervision was estimated in an uncontrolled clinical trial. Of the 39 participants, 12 (31%) remained cigarette free for 1 year, and 4 others (10%) had not smoked during the 3 months prior to the 1-year follow-up. Claims of cessation were verified by expired-air carbon monoxide measurement. Nearly all successful abstainers were able to achieve 48-hr cessation during their first week using the gum. This finding suggests that nicotine gum is best used to help the smoker quit abruptly, rather than as an aid in a tapering-off strategy. This study's smoking intervention program appears to provide a relatively low-cost method of improving the success rates among smokers who wish to quit.

Adolescent↗