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Biomedical subjects

S Kaufmann

Publications and source records attributed to S Kaufmann.

At least 19 recordsLinked to original sources
PubMed2006

Do intensive care patients need an individualized dosing regimen for levofloxacin?

OBJECTIVE: In general, the pharmacokinetics (PK) of antibiotics in intensive care unit (ICU) patients are known to differ from healthy subjects. These differences can pose challenges in developing appropriate dosing guidelines. The primary objective of this report was to characterize the disposition of levofloxacin in critically ill patients and to assess any relationships between patient covariates and the PK parameters. METHODS: 20 patients in the ICU were given levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were taken until 24 hours and assayed using HPLC. The concentration-time data were analyzed using population analysis with NONMEM. RESULTS: The data were described using a 2-compartment model. Creatinine clearance was determined to be a statistically significant predictor of variability in total levofloxacin clearance. For patients with higher levofloxacin clearance, the resulting efficacy for different strains of bacteria (expressed as free AUC/MIC ratios) suggested that for less sensitive pathogens, a dosage adjustment may be needed. CONCLUSION: A model describing the pharmacokinetics of levofloxacin in critically ill patients was developed. It was determined that creatinine clearance has a significant role in the disposition of levofloxacin. This may have significant implications in the clinical setting for identifying optimal dosage regimens for ICU patients.

Anti-Bacterial Agents↗
PubMed2002

A differential involvement of the shell and core subterritories of the nucleus accumbens of rats in attentional processes.

The nucleus accumbens comprises of two anatomically distinct subterritories: an inner core and an outer shell region. The distinct pattern of the core and shell input and output targets suggests that these two regions may mediate different behavioral processes. Using N-methyl-D-aspartate excitotoxic lesions in either the core or shell region, we investigated whether we can dissociate functionally these two subterritories. N-Methyl-D-aspartate-lesioned, sham-lesioned and non-operated animals were tested for locomotor activity in an open field and in two behavioral paradigms known to evaluate attentional deficits, namely the pre-pulse inhibition of the acoustic startle reflex and latent inhibition, measured in a two-way active avoidance paradigm. The shell-lesioned animals showed a small but significant hyperactivity in the open field when compared to the core-lesioned and to control animals. In the pre-pulse inhibition paradigm, core-lesioned animals demonstrated reduced pre-pulse inhibition to the two high pre-pulse intensities (80 dB[A], 84 dB[A]). In the active avoidance paradigm, whereas no lesion effects were detected in the non-pre-exposed groups, clear attenuation of latent inhibition was found in the shell-lesioned rats, in comparison to both core-lesioned and control rats, due to improved avoidance performance of the shell-pre-exposed group. From these results we suggest that the two subterritories of the nucleus accumbens are differentially involved in attention-related processes: the core lesion leads to significant disruption of pre-pulse inhibition while the shell lesion leads to heightened activity and significant attenuation of latent inhibition.

Acoustic Stimulation↗
PubMed2001

Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation.

STUDY DESIGN: A case report of anaerobic vertebral osteomyelitis after anal dilatation. OBJECTIVES: To present a patient with monomicrobial anaerobic vertebral osteomyelitis secondary to a previously undescribed source of infection. SUMMARY OF BACKGROUND DATA: A 17-year-old boy presented with low back pain 3 months after anal dilatation. METHODS: Physical examination, technetium-99m bone scan, plain radiograph, CT, and MRI studies of the lumbar spine were used to clinically diagnose lumbar osteomyelitis. Culture material from the involved disc was positive for Bacteroides fragilis. RESULTS: The patient recovered after 8 weeks of treatment with oral metronidazole. CONCLUSIONS: Bacteroides fragilis hematogenous osteomyelitis is a rare entity. This is the first reported case of such disease after anal dilatation.

Adolescent↗
PubMed2001

Influence of clay minerals on the hydrolysis of carbamate pesticides.

Using batch experiments, we investigated the influence of clay minerals (montmorillonite, beidellite, illite, and vermiculite) on the hydrolysis of five carbamate pesticides: carbosulfan, carbofuran, aldicarb, pirimicarb, and chlorpropham. Compared to the other minerals, montmorillonite had the strongest influence on the hydrolysis of these carbamates. Montmorillonite enhanced the hydrolysis of carbosulfan and aldicarb. In contrast, the hydrolysis of chlorpropham was inhibited by montmorillonite, probably because of its strong adsorption on montmorillonite. The hydrolysis of pirimicarb was not affected by montmorillonite. The presence of organic substances, phosphate, and fluoride in suspensions decreased the catalytic activity of montmorillonite. Surface acidity of montmorillonite and/or formation of surface chelates are probably the key factors of surface catalysis in the case of the hydrolysis of carbosulfan.

Adsorption↗
PubMed2001

Molecular cloning and characterization of WdPKS1, a gene involved in dihydroxynaphthalene melanin biosynthesis and virulence in Wangiella (Exophiala) dermatitidis.

1,8-Dihydroxynaphthalene (1,8-DHN) is a fungal polyketide that contributes to virulence when polymerized to 1,8-DHN melanin in the cell walls of Wangiella dermatitidis, an agent of phaeohyphomycosis in humans. To begin a genetic analysis of the initial synthetic steps leading to 1,8-DHN melanin biosynthesis, a 772-bp PCR product was amplified from genomic DNA using primers based on conserved regions of fungal polyketide synthases (Pks) known to produce the first cyclized 1,8-DHN-melanin pathway intermediate, 1,3,6,8-tetrahydroxynaphthalene. The cloned PCR product was then used as a targeting sequence to disrupt the putative polyketide synthase gene, WdPKS1, in W. dermatitidis. The resulting wdpks1Delta disruptants showed no morphological defects other than an albino phenotype and grew at the same rate as their black wild-type parent. Using a marker rescue approach, the intact WdPKS1 gene was then successfully recovered from two plasmids. The WdPKS1 gene was also isolated independently by complementation of the mel3 mutation in an albino mutant of W. dermatitidis using a cosmid library. Sequence analysis substantiated that WdPKS1 encoded a putative polyketide synthase (WdPks1p) in a single open reading frame consisting of three exons separated by two short introns. This conclusion was supported by the identification of highly conserved Pks domains for a beta-ketoacyl synthase, an acetyl-malonyl transferase, two acyl carrier proteins, and a thioesterase in the deduced amino acid sequence. Studies using a neutrophil killing assay and a mouse acute-infection model confirmed that all wdpks1Delta strains were less resistant to killing and less virulent, respectively, than their wild-type parent. Reconstitution of 1,8-DHN melanin biosynthesis in a wdpks1Delta strain reestablished its resistance to killing by neutrophils and its ability to cause fatal mouse infections.

Amino Acid Sequence↗
PubMed2000

Purification and characterization of perlucin and perlustrin, two new proteins from the shell of the mollusc Haliotis laevigata.

Two new proteins, named perlucin and perlustrin, with M(r) 17,000 and 13,000, respectively, were isolated from the shell of the mollusc Halotis laevigata (abalone) by ion-exchange chromatography and reversed-phase HPLC after demineralization of the shell in 10% acetic acid. The sequence of the first 32 amino acids of perlucin indicated that this protein belonged to a heterogeneous group of proteins consisting of a single C-type lectin domain. Perlucin increased the precipitation of CaCO(3) from a saturated solution, indicating that it may promote the nucleation and/or the growth of CaCO(3) crystals. With pancreatic stone protein (lithostathine) and the eggshell protein ovocleidin 17, this is the third C-type lectin domain protein isolated from CaCO(3) biominerals. This indicates that this type of protein performs an important but at present unrecognized function in biomineralization. Perlustrin was a minor component of the protein mixture and the sequence of the first 33 amino acids indicated a certain similarity to part of the much larger nacre protein lustrin A.

Amino Acid Sequence↗
PubMed1999

PICKLE is a CHD3 chromatin-remodeling factor that regulates the transition from embryonic to vegetative development in Arabidopsis.

The life cycle of angiosperms is punctuated by a dormant phase that separates embryonic and postembryonic development of the sporophyte. In the pickle (pkl) mutant of Arabidopsis, embryonic traits are expressed after germination. The penetrance of the pkl phenotype is strongly enhanced by inhibitors of gibberellin biosynthesis. Map-based cloning of the PKL locus revealed that it encodes a CHD3 protein. CHD3 proteins have been implicated as chromatin-remodeling factors involved in repression of transcription. PKL is necessary for repression of LEC1, a gene implicated as a critical activator of embryo development. We propose that PKL is a component of a gibberellin-modulated developmental switch that functions during germination to prevent reexpression of the embryonic developmental state.

Arabidopsis↗
PubMed1998

Iodine supplementation of laying hen feed: a supplementary measure to eliminate iodine deficiency in humans?

Iodine deficiency still exists in many countries worldwide, to a certain degree this is also true for Germany. Food of animal origin can be a good source for iodine depending on the feed. To investigate the possible use of laying hen feed enriched with iodine, we conducted a feeding experiment with 40 laying hens receiving feed with different amounts of iodine either as KIO3 or in the form of seaweed. Iodine concentration in eggs increased significantly depending on iodine intake after a 2 week period. Seaweed could also be used as an iodine source by the hens. A subsequent consumption study with 24 volunteers showed that eggs enriched with iodine can increase human's iodine excretion and therefore improve human's iodine supply. This new strategy is thought to accompany salt iodization programs, not to replace them.

Animals↗
PubMed1998

The relationship between follicular fluid aspirate volume and oocyte maturity in in-vitro fertilization cycles.

As a consequence of multiple follicular growth during ovarian stimulation for in-vitro fertilization (IVF), follicles of varying sizes often yield oocytes that vary in maturity and morphology of the oocyte-cumulus-corona complex. The objective of this prospective study was to explore the relationship between follicular fluid aspirate volume and the oocyte's developmental potential in an IVF treatment cycle. In total 9933 follicles were studied from 400 patients who underwent 535 consecutive IVF treatment cycles at St James's University Hospital, Leeds, UK, between February 1995 and February 1996. The volume of each individual follicle aspirated was recorded and related to the probability of obtaining an oocyte, its fertilizing capacity, the cleavage rate and the quality of embryos derived. We found no statistically significant difference in oocyte recovery rates between follicles with an aspirate volume < or = 1 ml and follicles with a volume > 1 ml. Although oocytes obtained from follicles with an aspirate volume > or = 1 ml showed a significantly lower fertilization rate, they went on to cleave at the same rate as oocytes obtained from larger follicles and resulted in embryos of comparable quality. Furthermore, there was no statistically significant difference in the implantation, clinical pregnancy or live birth rates per cycle between embryos derived from follicles with an aspirate volume < or = 1 ml and those derived from follicles with an aspirate volume > 1 ml. We conclude that follicular size and the oocyte's developmental potential in the stimulated ovary are not closely related and can be independent. This is in contrast to the Graafian follicle and the pre-ovulatory oocyte in the natural cycle.

Adult↗
PubMed1998

Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1.

Angiogenesis is essential in physiological processes including ovulation, implantation and pregnancy. One of the most potent regulators is the cytokine vascular endothelial growth factor (VEGF). We provide evidence for a novel pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples from normal volunteers (n = 10), but was undetectable in plasma from pregnant women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor in pregnancy-related samples, indicating the presence of VEGF-binding activity which was confirmed using biosensor and chromatographic techniques. Partial purification and protein sequencing indicated a novel soluble form of Flt-1 with a subunit size of 150 kDa. Normally present as a multimeric structure of approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and cord blood samples produced bands of the predicted sizes but failed to identify any additional RNA species, and possible reasons for this are discussed. Soluble Flt-1 may be important in regulating the actions of VEGF in angiogenesis and trophoblast invasion and may have therapeutic implications in diseases with inappropriate angiogenesis such as proliferative retinopathies and cancer.

Amino Acid Sequence↗
PubMed1997

Examining F-actin interaction with intact talin and talin head and tail fragment using static and dynamic light scattering.

We examined the binding kinetics of intact talin and talin head and tail fragment with F-actin at pH 7.0 and at low ionic strength. We observed by a transient kinetic method a fast followed by a slower binding process for intact talin and talin tail fragment with filamentous actin. The latter can be attributed to F-actin cross-linking and/or bundling, which was observed in cosedimentation assays as well as by low shear viscometry and electron microscopy [Zhang, J., Robson, R. M., Schmidt, J. M. & Stromer, M. H. (1996) Biochem. Biophys. Res. Commun. 218, 530-537]. This finding is supported by dynamic light scattering measurements, indicating changes in internal actin filament dynamics due to cross-linking/bundling events with intact talin and talin tail fragment. No binding of the talin head fragment with F-actin was detected by either method.

Actins↗
PubMed1997

[Improving the human iodine supply by iodination of swine feed].

Germany and several other countries are areas of severe iodine deficiency. In addition to iodized salt additional strategies to fight iodine deficiency exist. A promising possibility is the supplementation of feed with iodine, in order to increase its content in food of animal origin. In a feeding experiment 24 male castrated and female piglets of the cross breed Deutsche Landrasse x Pietrain were fed a high iodine supplemented diet. At a body weight of 100 kg the animals were slaughtered and the effect of the iodine supplementation on iodine content in the organs was studied. Animals receiving 30 mg iodine/kg feed showed significantly higher iodine contents in muscle, heart, kidney, liver, serum, fat and in the thyroidea than animals receiving no iodine supplementation. The iodine content in muscle and organs increased by a factor three to seven. Concerning meat quality and other slaughter parameters there was no difference between the two groups. This demonstrates that this strategy is in addition to iodized salt a possibility to reduce iodine deficiency.

Abattoirs↗
PubMed1996

Probing phosphatidylinositolphosphates and adenosinenucleotides on talin nucleated actin polymerization.

We have investigated the binding of PI, PIP and PIP2 to talin and the effect of phosphoinositides and adenosinenucleotides on talin-induced actin polymerization. At physiological salt concentrations, talin coprecipitates with liposomes when containing phosphoinositides but not when containing PI. The nucleating effect of talin as reflected by a twofold increase of fluorescence during the polymerization of actin labelled with NBD is not inhibited by phosphoinositides. The polymerization of ADP-actin versus ATP-actin was investigated in the presence and absence of talin by NBD fluorescence. ADP-actin nucleation induced by talin is comparably efficient as with ATP-actin. These experimental findings in summary have implications when evaluating the role of talin during cell activation.

Actins↗
PubMed1996

The thermodynamic control of protein binding to lipid bilayers for protein chromatography.

A new concept of charge-selective bioseparation with certain advantages over the established ion-exchange technique is reported. The procedure is based on the temperature-controlled creation and dispersion of domain structures in single phospholipid bilayers by means of the phase transition between the gel phase and the fluid phase of the bilayer. The bilayers are presented on a solid support of silica gel. Rather than altering the ionic strength of the buffer, protein elution is accomplished by a change of the chromatography column temperature. The application of temperature gradients improves the protein selectivity of phase transition chromatography.

Animals↗
PubMed1996

Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo.

Platelet-derived growth factor (PDGF) is postulated to play a role in the pathophysiology of pulmonary fibrosis. Recombinant human PDGF-BB administered as a single intratracheal injection in rats causes an increase in peribronchial and perivascular stromal cells on days 2 and 3 after injection as evaluated by hematoxylin and eosin histology and 5-bromodeoxyuridine incorporation. Proliferation of bronchial epithelial cells and arterial smooth muscle cells, although not evident by routine histological examination alone, is detected on days 2 and 3 by increased 5-bromodeoxyuridine incorporation. A mild increase in 5-bromodeoxyuridine labeling is observed in peripheral alveolar parenchyma after injection of PDGF. The proliferative peribronchial and perivascular mesenchymal cells appear by light microscopic and ultrastructural criteria to be fibroblasts that are immunoreactive for vimentin but negative for alpha-smooth muscle actin and desmin. Daily intratracheal injection of PDGF-BB for 3 days causes a slightly more pronounced peribronchial and perivascular spindle cell proliferation accompanied by collagen deposition as evaluated by Masson's trichrome stain. PDGF-induced increases in cellularity and collagen resolve within 5 days after the last PDGF injection. In conclusion, intratracheal injection of PDGF-BB causes transient proliferation of pulmonary mesenchymal and epithelial cells accompanied by collagen deposition.

Actins↗
PubMed1995

Determination of the affinity of talin and vinculin to charged lipid vesicles: a light scatter study.

Recent experimental findings have demonstrated that both talin and vinculin bind to phospholipids and insert into the hydrophobic region of lipid membranes. Here, we show that the light scatter method can be used for measuring the affinity of proteins to phospholipid membranes. Large unilamellar DMPC/DMPG vesicles were produced by the extrusion technique (LUVETs). We have used repeated heating/cooling scans between 15 degrees C and 35 degrees C to ensure protein-lipid interaction/insertion. A molar affinity of talin, K = 2.9 x 10(6) M-1 and of vinculin, K = 3.3 x 10(5) M-1 to lipid vesicles, respectively, was determined from the plot; light scatter signal at 380 nm against protein concentrations by fitting the term, ln (Io/I-1) = A-K x c to the data.

Dimyristoylphosphatidylcholine↗
PubMed1994

Identification of functional domains in the cytoskeletal protein talin.

The cytoskeletal protein talin potentially plays a key role in actin-membrane linkage. It is able to nucleate actin filament growth in vitro while binding simultaneously to lipid bilayers. Thrombin digestion of human platelet talin yields tow polypeptide domains of 200 kDa and 47 kDa. We have purified these fragments and analyzed their functional properties: the 200-kDa fragment was active in nucleating actin filament formation and reduced the viscosity of filamentous actin, comparable to the effects of the intact protein. The 47-kDa fragment was inactive in this respect. However, the 47-kDa polypeptide, but not the 200-kDa fragment, interacted specifically with large liposomes containing acidic phospholipids. This is demonstrated by selective, hydrophobic photolabeling of the 47-kDa fragment using phosphatidylserine liposomes containing trace amounts of a photoactivable phospholipid analogue and by selective co-sedimentation of this domain with the liposomes. The 200-kDa fragment, whether alone or in conjunction with the small fragment, neither incorporated significant amounts of label nor co-sedimented with the liposomes. We thus are able to attribute specialized functions to distinct domains on the talin molecule. These enable the protein to interact simultaneously with actin filaments and lipid membranes.

Actins↗