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Biomedical subjects

P Kuhn

Publications and source records attributed to P Kuhn.

At least 19 recordsLinked to original sources
PubMed2006

Phosphorus-phosphorus coupling in a diphosphine with a ten bond P...P separation.

The large, unsymmetrical diphosphine 5,11,17,23-tetra-tert-butyl-25,26-bis(diphenylphosphinomethoxy)-27(or 28)-benzoyloxy-28(or 27)-hydroxycalix[4]arene, in which the phosphorus atoms are separated by ten bonds, was prepared by monobenzoylation of 5,11,17,23-tetra-tert-butyl-25,26-bis(diphenylphosphinoylmethoxy)-27,28-bis(hydroxy)calix[4]arene, followed by reduction with phenyl silane. Its molecular structure has been determined by X-ray crystallography. In the solid state, the phosphorus atoms are separated by 5.333(1) A. NMR investigations reveal an unexpected "through-space"J(PP') coupling constant of 8.0 Hz and also show that, in solution, the calixarene is conformationally mobile, the phenoxy ring flipping rapidly through the calixarene annulus. The spatial proximity of the two phosphorus atoms was further demonstrated by the ease of obtaining the cis-chelate complex [Pd(eta3-C3H4Me)(THF)2]BF4 (THF = tetrahydrofuran).

Journal Article↗
PubMed2004

[Injectable therapy for urinary incontinence: a review].

Trans- or periurethral bladder neck injections are minimal invasive therapies for stress urinary incontinence which can be performed under local anaesthetic as an outpatient procedure. So far the best documented substance is collagen of bovine origin but other substances as silicone, autologous fat, chondrocytes and ethylenevinylalcohol are available. Success rates are between 60 and 80% with deteriorating long term results of approximately 30% requiring reinjection usually after 18 to 24 months.

Adipose Tissue↗
PubMed2004

[Secondary surfactant deficiencies].

Preterm babies born before the 33rd week of gestation often exhibit primary surfactant deficiency responsible for the respiratory distress syndrome or hyaline membrane disease. In that situation, there is a limited and insufficient production of surfactant by type II alveolar cells of the lung due to immaturity. Secondary surfactant deficiencies occur in patients with prior normal surfactant synthesis and can be related to sepsis, hypoxia, ventilator induced lung injury or surfactant inhibition by a variety of substances reaching the alveolar spaces. They occur in full-term newborns with meconium aspiration syndrome, acute respiratory distress syndrome and congenital diaphragmatic hernia. In children and adults, acute respiratory distress syndrome and respiratory syncytial virus bronchiolitis can be responsible. In prematures they occur after the initial primary deficiency during pulmonary hemorrhage, pneumonia and bronchopulmonary dysplasia. Treatment with exogenous surfactant may be beneficial. There is a need for randomized controlled studies for evaluation of this treatment. Next generation of surfactants containing recombinant surfactant protein or synthetic peptides appear as promising agents in these situations of secondary surfactant deficiencies.

Adult↗
PubMed2004

[Secondary surfactant deficiencies in extremely low birth weight premature infants].

Primary deficiency of surfactant is responsible for the respiratory distress syndrome and concerns premature neonates born before 33 weeks of gestation. However, newborns may develop respiratory disorders related to a secondary deficiency or dysfunction of surfactant. We report the course of three extremely low birth weight premature infants who experienced clinical respiratory decompensation at two weeks and showed a marked improvement after exogenous natural surfactant administration.

Humans↗
PubMed2004

The effect of light on the settlement of the salmon louse, Lepeophtheirus salmonis, on Atlantic salmon, Salmo salar L.

The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic copepod that infests both wild and farmed salmonid fish. Salmon lice are a major disease problem in the farming of Atlantic salmon, Salmo salar L., and the possibility of salmon lice playing a role in the decline of wild anadromous stocks has also been raised. Lepeophtheirus salmonis can detect a range of stimuli (pressure/moving water, chemicals and light) in the external environment. However, the response thresholds to various stimuli, and the spatial and temporal scales over which they operate in the context of host location, are largely unknown. In this context, we attempted to determine whether salmon lice copepodids settle onto hosts more effectively, or at different locations on the fish's body, under different qualities of light. Lice settlement trials were conducted under three lighting conditions; L1: unpolarized under ultraviolet A (UVA)-through visible; L2: unpolarized without UVA (control); L3: 100% linearly polarized without UVA. A dark control was also conducted. No statistically significant difference in lice settlement was found. While changes in light intensity are involved in host detection at spatial scales on the order of metres, the results presented here suggest that it is not the primary sensory modality underlying host location at smaller spatial scales (cm to mm).

Animals↗
PubMed2003

Effects of antenatal antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis. A retrospective study over five years.

BACKGROUND: Recommendations for the use of antenatal antibiotics have been widely implemented in the past few years, notably to prevent group B streptococcal disease or to prolong pregnancy in the case of preterm premature rupture of the membranes. OBJECTIVES: We designed a retrospective study to assess the potential effects of this increasing use of antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS). METHODS: All neonates referred to our department for suspected EONS from January 1 1995 through December 31 1999 were included. Antenatal antibiotic exposure together with clinical and microbiological data from the neonatal period were gathered and analyzed on a yearly basis. RESULTS: Of the 485 newborns who met the inclusion criteria, there were 101 cases of culture-confirmed sepsis; 339 cases of suspected sepsis and 69 cases of confirmed sepsis involved children born in the hospital, among a total of 16,627 live births registered in our center over the study period. The overall incidence of EONS dropped from 6.8 to 0.6/1,000 births between 1995 and 1999 (p < 0.001), but the rate of group B streptococcal infection decreased much more rapidly than that of non-group B streptococcal infection. We observed a trend towards the emergence of ampicillin-resistant Escherichia coli strains, which were isolated in seven cases. Among E. COLI infections, ampicillin resistance was statistically linked with antenatal antibiotic use (p = 0.025). We also delineated several risk factors associated with these infections. CONCLUSION: In our center, antenatal antibiotic treatment was effective in reducing the incidence of EONS, but this benefit may come at the cost of favoring the emergence of ampicillin-resistant organisms causing severe neonatal infections. Antenatal and postnatal antibiotic treatment strategies should take this adverse effect into account.

Ampicillin Resistance↗
PubMed2001

Crystal structure of the 100 kDa arsenite oxidase from Alcaligenes faecalis in two crystal forms at 1.64 A and 2.03 A.

BACKGROUND: Arsenite oxidase from Alcaligenes faecalis NCIB 8687 is a molybdenum/iron protein involved in the detoxification of arsenic. It is induced by the presence of AsO(2-) (arsenite) and functions to oxidize As(III)O(2-), which binds to essential sulfhydryl groups of proteins and dithiols, to the relatively less toxic As(V)O(4)(3-) (arsenate) prior to methylation. RESULTS: Using a combination of multiple isomorphous replacement with anomalous scattering (MIRAS) and multiple-wavelength anomalous dispersion (MAD) methods, the crystal structure of arsenite oxidase was determined to 2.03 A in a P2(1) crystal form with two molecules in the asymmetric unit and to 1.64 A in a P1 crystal form with four molecules in the asymmetric unit. Arsenite oxidase consists of a large subunit of 825 residues and a small subunit of approximately 134 residues. The large subunit contains a Mo site, consisting of a Mo atom bound to two pterin cofactors, and a [3Fe-4S] cluster. The small subunit contains a Rieske-type [2Fe-2S] site. CONCLUSIONS: The large subunit of arsenite oxidase is similar to other members of the dimethylsulfoxide (DMSO) reductase family of molybdenum enzymes, particularly the dissimilatory periplasmic nitrate reductase from Desulfovibrio desulfuricans, but is unique in having no covalent bond between the polypeptide and the Mo atom. The small subunit has no counterpart among known Mo protein structures but is homologous to the Rieske [2Fe-2S] protein domain of the cytochrome bc(1) and cytochrome b(6)f complexes and to the Rieske domain of naphthalene 1,2-dioxygenase.

Alcaligenes↗
PubMed2001

Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland.

OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation in Germany, Austria and Switzerland. METHODS: This was a multicenter study of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. All the sonographers involved in the study had received The Fetal Medicine Foundation Certificate of Competence in the 10-14-week scan. Fetal nuchal translucency thickness and crown-rump length were measured in 23 805 singleton pregnancies with live fetuses. In each case the risk for trisomy 21 was estimated on the basis of maternal age and fetal nuchal translucency thickness for crown-rump length with the use of The Fetal Medicine Foundation's software. The distribution of estimated risk was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 was calculated. RESULTS: Fetal nuchal translucency thickness was successfully measured in all 23 805 pregnancies and outcome was available in 21 959. The median maternal age was 33 (range 15-49) years and in 7935 (36.1%) the age was 35 years or greater. The median gestation at screening was 12 (10-14) weeks and the median fetal crown-rump length was 61 (range 38-84) mm. The estimated risk for trisomy 21 based on maternal age and fetal nuchal translucency thickness for crown-rump length was 1 in 300 or greater in 13.0% (2800 of 21 475) normal pregnancies, in 87.6% (184 of 210) of those with trisomy 21 and in 87.2% (239 of 274) with other chromosomal defects. CONCLUSIONS: In Germany, Austria and Switzerland the results of screening for chromosomal defects by measurement of fetal nuchal translucency thickness, in centers with appropriately qualified sonographers and using The Fetal Medicine Foundation's software, are similar to those reported in the UK using the same methodology.

Austria↗
PubMed2000

Structure of a thioredoxin-like [2Fe-2S] ferredoxin from Aquifex aeolicus.

The 2.3 A resolution crystal structure of a [2Fe-2S] cluster containing ferredoxin from Aquifex aeolicus reveals a thioredoxin-like fold that is novel among iron-sulfur proteins. The [2Fe-2S] cluster is located near the surface of the protein, at a site corresponding to that of the active-site disulfide bridge in thioredoxin. The four cysteine ligands are located near the ends of two surface loops. Two of these ligands can be substituted by non-native cysteine residues introduced throughout a stretch of the polypeptide chain that forms a protruding loop extending away from the cluster. The presence of homologs of this ferredoxin as components of more complex anaerobic and aerobic electron transfer systems indicates that this is a versatile fold for biological redox processes.

Amino Acid Sequence↗
PubMed2000

Conformational flexibility of B-DNA at 0.74 A resolution: d(CCAGTACTGG)(2).

The affinity and specificity of a ligand for its DNA site is a function of the conformational changes between the isolated and complexed states. Although the structures of a hydroxypyrrole-imidazole-pyrrole polyamide dimer with 5'-CCAGTACTGG-3' and the trp repressor recognizing the sequence 5'-GTACT-3' are known, the baseline conformation of the DNA site would contribute to our understanding of DNA recognition by these ligands. The 0.74 A resolution structure of a B-DNA double helix, 5'-CCAGTACTGG-3', has been determined by X-ray crystallography. Six of the nine phosphates, two of four bound calcium ions and networks of water molecules hydrating the oligonucleotide have alternate conformations. By contrast, nine of the ten bases have a single, unique conformation with hydrogen atoms visible in most cases. The polyamide molecules alter the geometry of the phosphodiester backbone, and the water molecules mediating contacts in the trp repressor/operator complex are conserved in the unliganded DNA. Furthermore, the multiple conformational states, ions and hydration revealed by this ultrahigh resolution structure of a B-form oligonucleotide are potentially general considerations for understanding DNA-binding affinity and specificity by ligands.

Bacterial Proteins↗
PubMed2000

Crystal structure of the complex of brugia malayi cyclophilin and cyclosporin A.

The resistance of the human parasite Brugia malayi to the antiparasitic activity of cyclosporin A (CsA) may arise from the presence of cyclophilins with relatively low affinity for the drug. The structure of the complex of B. malayi cyclophilin (BmCYP-1) and CsA, with eight independent copies in the asymmetric unit, has been determined at a resolution of 2.7 A. The low affinity of BmCYP-1 for CsA arises from incomplete preorganization of the binding site so that the formation of a hydrogen bond between His132 of BmCYP-1 and N-methylleucine 9 of CsA is associated with a shift in the backbone of approximately 1 A in this region.

Amino Acid Sequence↗
PubMed2000

[Phrenic nerve paralysis of obstetrical origin: favorable course using continuous positive airway pressure].

INTRODUCTION: Isolated diaphragmatic paralysis due to obstetrical factors is rare and therapeutic management modalities are not quite clear. CASE REPORT: A neonate born by breech delivery presented with respiratory distress due to isolated paralysis of the right hemidiaphragm. The clinical course was progressive, his condition worsening with oxygen supplementation. Continuous positive airway pressure (CPAP) delivered via a nasal cannula was started in the one-month-old child, inducing gradual improvement towards recovery at the age of two months and a half. CONCLUSION: Non-invasive nasal CPAP should be proposed for the treatment of phrenic nerve obstetrical palsy before introducing more invasive ventilation techniques. Surgical plication should be delayed until the child reaches the age of at least three months.

Birth Injuries↗
PubMed2000

A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling.

Guanine nucleotide dissociation inhibitor (GDI) is a 55-kDa protein that functions in vesicular membrane transport to recycle Rab GTPases. We have now determined the crystal structure of bovine alpha-GDI at ultra-high resolution (1.04 A). Refinement at this resolution highlighted a region with high mobility of its main-chain residues. This corresponded to a surface loop in the primarily alpha-helical domain II at the base of alpha-GDI containing the previously uncharacterized sequence-conserved region (SCR) 3A. Site-directed mutagenesis showed that this mobile loop plays a crucial role in binding of GDI to membranes and extraction of membrane-bound Rab. This domain, referred to as the mobile effector loop, in combination with Rab-binding residues found in the multi-sheet domain I at the apex of alpha-GDI may provide flexibility for recycling of diverse Rab GTPases. We propose that conserved residues in domains I and II synergize to form the functional face of GDI, and that domain II mediates a critical step in Rab recycling during vesicle fusion.

Amino Acid Motifs↗
PubMed2000

Automation of X-ray crystallography.

Structure-based biological discovery is entering a new era with the development of industrialized macromolecular structure determination pipelines. Intense, highly focused X-rays from integrated synchrotron radiation beam lines combined with significant advances in protein expression, purification, and micro-crystallization automation allow for the full streamlining of the traditionally tedious and time consuming process of determining the three dimensional structures of macromolecules.

Automation↗
PubMed2000

The atomic resolution structure of bucandin, a novel toxin isolated from the Malayan krait, determined by direct methods.

Bucandin is a novel presynaptic neurotoxin isolated from Bungarus candidus (Malayan krait). It has the unique property of enhancing presynaptic acetylcholine release and represents a family of three-finger toxins with an additional disulfide in the first loop. There are no existing structures from this sub-category of three-finger toxins. The X-ray crystal structure of bucandin has been determined by the Shake-and-Bake direct-methods procedure. The resulting electron-density maps were of outstanding quality and allowed the automated tracing of 61 of the 63 amino-acid residues, including their side chains, and the placement of 48 solvent molecules. The 0.97 A resolution full-matrix least-squares refinement converged to a crystallographic R factor of 12.4% and the final model contains 118 solvent molecules. This is the highest resolution structure of any member of the three-finger toxin family and thus it can serve as the best model for other members of the family. Furthermore, the structure of this novel toxin will help in understanding its unique ability to enhance acetylcholine release. The unique structure resulting from the fifth disulfide bond residing in the first loop improves the understanding of other toxins with a similar arrangement of disulfide bonds.

Amino Acid Sequence↗