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R Kahn

Publications and source records attributed to R Kahn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Endovascular grafts in the treatment of thoracic aortic aneurysms and pseudoaneurysms.

The purpose of this study was to describe our experience with balloon and self-expanding endovascular grafts for the management of thoracic aortic lesions. Between February 1997 and June 1998, 20 endovascular grafts were implanted in 14 patients for the treatment of thoracic aortic aneurysms and pseudoaneurysms. Endovascular procedures were performed using one of four different devices: (1) Dacron-covered balloon-expandable Palmaztrade mark stent, (2) balloon-expandable Palmaz stent-PTFE graft prosthesis (BE-PS), (3) self-expanding internally supported Nitinol Dacron prosthesis (Vanguardtrade mark SE-V), and (4) self-expanding externally supported Nitinol PTFE prosthesis (Excludertrade mark SE-E). The results show that endovascular grafting represents a potentially important alternative therapy to open repair of the thoracic aorta. Self-expanding devices were, in our experience, easier to use and more accurately deployed.

Adult↗
PubMed2000

Interaction between the lipoamide-containing H-protein and the lipoamide dehydrogenase (L-protein) of the glycine decarboxylase multienzyme system 2. Crystal structures of H- and L-proteins.

The glycine decarboxylase complex consists of four different component enzymes (P-, H-, T- and L-proteins). The 14-kDa lipoamide-containing H-protein plays a pivotal role in the complete sequence of reactions as its prosthetic group (lipoic acid) interacts successively with the three other components of the complex and undergoes a cycle of reductive methylamination, methylamine transfer and electron transfer. With the aim to understand the interaction between the H-protein and its different partners, we have previously determined the crystal structure of the oxidized and methylaminated forms of the H-protein. In the present study, we have crystallized the H-protein in its reduced state and the L-protein (lipoamide dehydrogenase or dihydrolipoamide dehydrogenase). The L-protein has been overexpressed in Escherichia coli and refolded from inclusion bodies in an active form. Crystals were obtained from the refolded L-protein and the structure has been determined by X-ray crystallography. This first crystal structure of a plant dihydrolipoamide dehydrogenase is similar to other known dihydrolipoamide dehydrogenase structures. The crystal structure of the H-protein in its reduced form has been determined and compared to the structure of the other forms of the protein. It is isomorphous to the structure of the oxidized form. In contrast with methylaminated H-protein where the loaded lipoamide arm was locked into a cavity of the protein, the reduced lipoamide arm appeared freely exposed to the solvent. Such a freedom is required to allow its targeting inside the hollow active site of L-protein. Our results strongly suggest that a direct interaction between the H- and L-proteins is not necessary for the reoxidation of the reduced lipoamide arm bound to the H-protein. This hypothesis is supported by biochemical data [Neuburger, M., Polidori, A.M., Piètre, E., Faure, M., Jourdain, A., Bourguignon, J., Pucci, B. & Douce, R. (2000) Eur. J. Biochem. 267, 2882-2889] and by small angle X-ray scattering experiments reported herein.

Amino Acid Oxidoreductases↗
PubMed2000

Low-resolution phase information in multiple-wavelength anomalous solvent contrast variation experiments.

The basic theory and principles of the multiple-wavelength anomalous solvent-contrast (MASC) method are introduced as a contrast-variation technique for generating low-resolution crystallographic phase information on the envelope of a macromolecule. Experimental techniques and practical considerations concerning the choice of anomalous scatterer, sample preparation and data acquisition are discussed. Test cases of crystals of three proteins of differing molecular weights from 14 kDa through to 173 kDa are illustrated. Methods for extracting the moduli of the anomalous structure factors from the MASC data are briefly discussed and the experimental results are compared with the known macromolecular envelopes. In all cases, the lowest resolution shells exhibit very large anomalous signals which diminish at higher resolution, as expected by theory. However, in each case the anomalous signal persists at high resolution, which is strong evidence for ordered sites of the anomalous scatterers. For the smaller two of these proteins the heavy-atom parameters could be refined for some of these sites. Finally, a novel method for phasing the envelope structure-factor moduli is presented. This method takes into account the relatively low number of observations at low resolution and describes the macromolecular envelope with a small number of parameters by presuming that the envelope is a compact domain of known volume. The parameterized envelope is expressed as a linear combination of independent functions such as spherical harmonics. Phasing starts from solutions of a sphere in the unit cell after positional refinement from random trials and the parameters describing the envelope are then refined against the data of structure-factor moduli. The preliminary results using simulated data show that the method can be used to reconstruct the correct macromolecular envelope and is able to discriminate against some false solutions.

Aldose-Ketose Isomerases↗
PubMed2000

A national survey of training in substance use disorders in residency programs.

OBJECTIVE: To determine the amount of formal training in substance use disorders that occurs in selected residency programs and to identify the perceived barriers to such training. METHOD: A national survey was conducted of program directors in emergency medicine, family medicine, internal medicine, obstetrics/gynecology, osteopathic medicine, pediatrics and psychiatry. In 1997, program directors were mailed a brief survey to determine the extent to which required training in substance use disorders occurred and the median number of hours devoted to substance use disorders training. Follow-up telephone surveys were conducted with faculty designated in the survey as responsible for substance-related disorders training to determine type of training and barriers to training. RESULTS: Of 1,831 program directors, 1,183 (64.6%) responded to the brief survey. The percentage of programs with required substance use disorders training ranged from 31.8% in pediatrics to 95.0% in psychiatry, with 56.3% for all programs combined. The median number of curricular hours ranged from 3 (emergency medicine and OB/GYN) to 12 (family medicine). Time was perceived to be the most common barrier to additional training. CONCLUSIONS: Consistent training for all residents in the initial diagnosis and management of substance use disorders has not been achieved. New strategies that integrate into existing residency structures are needed to improve substance use disorders training. Faculty development in substance use disorders and review of current substance use disorders training as part of the residency review process should facilitate this endeavor.

Alcoholism↗
PubMed2000

Anomalous X-ray diffraction with soft X-ray synchrotron radiation.

Anomalous diffraction with soft X-ray synchrotron radiation opens new possibilities in protein crystallography and materials science. Low-Z elements like silicon, phosphorus, sulfur and chlorine become accessible as new labels in structural studies. Some of the heavy elements like uranium exhibit an unusually strong dispersion at their M(V) absorption edge (lambdaMV = 3.497 A, E(MV) = 3545 eV) and so does thorium. Two different test experiments are reported here showing the feasibility of anomalous X-ray diffraction at long wavelengths with a protein containing uranium and with a salt containing chlorine atoms. With 110 electrons the anomalous scattering amplitude of uranium exceeds by a factor of 4 the resonance scattering of other strong anomalous scatterers like that of the lanthanides at their L(III) edge. The resulting exceptional phasing power of uranium is most attractive in protein crystallography using the multi-wavelength anomalous diffraction (MAD) method. The anomalous dispersion of an uranium derivative of asparaginyl-tRNA synthetase (hexagonal unit cell; a = 123.4 A, c = 124.4 A) has been measured for the first time at 4 wavelengths near the M(V) edge using the beamline ID1 of ESRF (Grenoble, France). The present set up allowed to measure only 30% of the possible reflections at a resolution of 4 A, mainly because of the low sensitivity of the CCD detector. In the second experiment, the dispersion of the intensity of 5 X-ray diffraction peaks from pentakismethylammonium undecachlorodibismuthate (PMACB, orthorhombic unit cell; a = 13.003 A, b = 14.038 A, c = 15.450 A) has been measured at 30 wavelengths near the K absorption edge of chlorine (lambdaK = 4.397 A, EK= 2819.6 eV). All reflections within the resolution range from 6.4 A to 3.4 A expected in the 20 degree scan were observed. The chemical state varies between different chlorine atoms of PMACB, and so does the dispersion of different Bragg peaks near the K-edge of chlorine. The results reflect the performance of the beamline ID1 of ESRF at wavelengths beyond 3 A at the end of 1998. A gain by a factor 100 for diffraction experiments with 4.4 A photons was achieved in Autumn 1999 when two focusing mirrors had been added to the X-ray optics. Further progress is expected from area detectors more sensitive to soft X-rays. Both CCD detectors and image plates would provide a gain of two orders of measured intensity. Image plates would have the additional advantage that they can be bent cylindrically and thus cover a larger solid angle in reciprocal space. In many cases, samples need to be cooled: closed and open systems are presented. A comparison with the state of art of soft X-ray diffraction, as it had been reached at HASYLAB (Hamburg, Germany), and as it is developing at the Brookhaven National Laboratory (USA), is given.

Amino Acyl-tRNA Synthetases↗
PubMed1999

Multiwavelength anomalous solvent contrast (MASC): derivation of envelope structure-factor amplitudes and comparison with model values.

A previous article [Fourme et al. (1995). J. Synchrotron Rad. 2, 36-48] presented the theoretical foundations of MASC, a new contrast-variation method using multiwavelength anomalous scattering, and reported the first experimental results. New experiments have been conducted both at the ESRF (Grenoble, France) and at LURE-DCI (Orsay, France), using cryocooled crystals of three proteins of known structures and very different molecular weights. Amplitudes of {GammaT(h)}, the 'normal' structure factors of the anomalously scattering part of the crystal including the solvent zone and the ordered anomalous scattering sites (if any), have been extracted from multiwavelength data. In the very low resolution range (d >/= 20 A), the agreement between experimental {GammaT(h)} and model values calculated from the bulk solvent is all the more satisfactory since the molecular weight of the protein is high. For spacings between 10 and 20 A, the agreement between experimental {GammaT(h)} and model values is also satisfactory if one takes into account ordered anomalous scatterer sites. Such sites have been found in the three cases.

Aldose-Ketose Isomerases↗
PubMed1999

International child health electives for pediatric residents.

BACKGROUND: International child health (ICH) electives can strengthen the skills and shape the values of pediatric residents. Much can be learned from the literature on ICH electives during medical school. Yet there is little published information regarding ICH electives during residency, nor do educational guidelines for such electives exist. OBJECTIVES: To describe existing ICH electives among pediatric residency programs and to develop guidelines for ICH electives during residency training. PARTICIPANTS AND METHODS: A survey of 248 pediatric residency programs in the United States, Canada, and Puerto Rico was conducted in November 1995. Consensus guidelines were developed by the executive committee of the American Academy of Pediatrics (AAP) Section on International Child Health. Consensus was achieved via full agreement among the 11 committee members. RESULTS: Survey response rate was 65%. International child health electives were offered by 25% of respondents. Most had no formal educational structure. An additional 42% of respondents indicated interest in ICH electives and requested more information. The AAP consensus guidelines for ICH electives focus on 4 principles: prerequisites, preceptorship, preparation, and evaluation. The guidelines are based on a conceptual framework that emphasizes reciprocity and continuity. CONCLUSIONS: While only 25% of pediatric residency programs currently offer ICH electives, many more express an interest in doing so. Educational structure for such electives is important and lacking. The AAP consensus guidelines provide a template for meaningful ICH experiences during pediatric residency. These guidelines may be applicable to other specialties as well.

Education, Medical, Graduate↗
PubMed1999

Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51.

CYP51s form the only family of P450 proteins conserved in evolution from prokaryotes to fungi, plants and mammals. In all eukaryotes, CYP51s catalyse 14alpha-demethylation of sterols. We have recently isolated two CYP51 cDNAs from sorghum [Bak, S., Kahn, R.A., Olsen, C. E. & Halkier, B.A. (1997) Plant J. 11, 191-201] and wheat [Cabello-Hurtado, F., Zimmerlin, A., Rahier, A., Taton, M., DeRose, R., Nedelkina, S., Batard, Y., Durst, F., Pallett, K.E. & Werck-Reichhart, D. (1997) Biophys. Biochem. Res. Commun. 230, 381-385]. Wheat and sorghum CYP51 proteins show a high identity (92%) compared with their identity with their fungal and mammalian orthologues (32-39%). Data obtained with plant microsomes have previously suggested that differences in primary sequences reflect differences in sterol pathways and CYP51 substrate specificities between animals, fungi and plants. To investigate more thoroughly the properties of the plant CYP51, the wheat enzyme was expressed in yeast strains overexpressing different P450 reductases as a fusion with either yeast or plant (sorghum) membrane targeting sequences. The endogenous sterol demethylase gene (ERG11) was then disrupted. A sorghum-wheat fusion protein expressed with the Arabidopsis thaliana reductase ATR1 showed the highest level of expression and activity. The expression induced a marked proliferation of microsomal membranes so as to obtain 70 nmol P450.(L culture)-1, with CYP51 representing 1.5% of microsomal protein. Without disruption of the ERG11 gene, the expression level was fivefold reduced. CYP51 from wheat complemented the ERG11 disruption, as the modified yeasts did not need supplementation with exogenous ergosterol and grew normally under aerobic conditions. The fusion plant enzyme catalysed 14alpha-demethylation of obtusifoliol very actively (Km,app = 197 microm, kcat = 1.2 min-1) and with very strict substrate specificity. No metabolism of lanosterol and eburicol, the substrates of the fungal and mammalian CYP51s, nor metabolism of herbicides and fatty acids was detected in the recombinant yeast microsomes. Surprisingly lanosterol (Ks = 2.2 microM) and eburicol (Ks = 2.5 microm) were found to bind the active site of the plant enzyme with affinities higher than that for obtusifoliol (Ks = 289 microM), giving typical type-I spectra. The amplitudes of these spectra, however, suggested that lanosterol and eburicol were less favourably positioned to be metabolized than obtusifoliol. The recombinant enzyme was also used to test the relative binding constants of two azole compounds, LAB170250F and gamma-ketotriazole, which were previously reported to be potent inhibitors of the plant enzyme. The Ks of plant CYP51 for LAB170250F (0.29 microM) and gamma-ketotriazole (0.40 microM) calculated from the type-II sp2 nitrogen-binding spectra were in better agreement with their reported effects as plant CYP51 inhibitors than values previously determined with plant microsomes. This optimized expression system thus provides an excellent tool for detailed enzymological and mechanistic studies, and for improving the selectivity of inhibitory molecules.

Amino Acid Sequence↗
PubMed1999

Networks of persons with syphilis and at risk for syphilis in Louisiana: evidence of core transmitters.

BACKGROUND AND OBJECTIVES: Differences in sociodemographic attributes and healthcare access may explain differences in regional sexually transmitted disease rates but don't fully explain why syphilis persists disproportionately in certain populations. GOAL OF THIS STUDY: To understand the behavioral epidemiology of syphilis, we conducted a social network analysis of persons with syphilis and their contacts and developed and applied a definition of core transmitters. STUDY DESIGN: We interviewed 10 index persons with primary or secondary untreated syphilis and 80 of their named sexual and social contacts. RESULTS: Fourteen (16%) of 90 interviewed persons met the definition of core transmitters, 9 of whom had past or current syphilis. The other interviewed persons had only moderately risky behaviors. Seventy-eight (42%) of the network sexual contacts were connected directly or indirectly to a core transmitter. CONCLUSION: This analysis suggests that syphilis transmission is maintained by a community with a small percentage of high-risk persons centrally placed amidst a larger group with moderately risky behavior.

Adult↗
PubMed1999

Purification, crystallization and preliminary X-ray analysis of catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa.

The catabolic ornithine carbamoyltransferase (OTCase) from Pseudomonas aeruginosa exhibits allosteric behaviour, with two conformational states of the molecule: an active R form and an inactive T form. The enzyme is a dodecamer with a molecular mass of 455700 Da. Three crystal forms have been obtained. Crystals of allosteric state T are rhombohedral, belonging to the R3 space group, with hexagonal unit-cell parameters a = b = 180.6, c = 122.0 A. They diffract to a resolution of 4.5 A. Two crystal forms for allosteric state R have been obtained, with hexagonal and cubic symmetries. Hexagonal crystals, which diffract to a resolution of 3. 4 A, belong to the space group P6(3) with unit-cell parameters a = b = 140.8, c = 145.6 A. The cubic crystals belong to space group I23, with unit-cell parameter a = 134.32 A and diffract to a resolution better than 2.5 A. In all crystal forms, the dodecamer exhibits a 23 point-group symmetry.

Bacterial Proteins↗
PubMed1999

Hepatic actinomycosis. A case report.

A case of hepatic actinomycosis contracted one year after removal of an intrauterine device during ongoing Actinomyces cervicitis is reported. During active disease, lymphocytes from the apparently fully immunocompetent patient were able to proliferate but not to produce the proinflammatory lymphokine gamma-interferon in response to Actinomyces antigen. This ability was only partly restored during antibiotic therapy.

Actinomycosis↗
PubMed1999

Who teaches residents about the prevention and treatment of substance use disorders? A national survey.

BACKGROUND: Studies indicate that physicians are poorly prepared to identify and treat tobacco, alcohol, and drug use disorders. Several faculty development programs have been created to increase the number of residency teaching faculty with expertise in this area. There is limited information, however, on those who currently teach residents about these problems and whether there is a need for additional faculty development programs. METHODS: We conducted a 2-stage national survey of faculty who teach residents about substance use problems. First, residency directors from 7 specialties (family medicine, psychiatry, internal medicine, pediatrics, obstetrics and gynecology, emergency medicine, and osteopathy) responded to a mailed questionnaire asking them to identify faculty who teach residents about substance use disorders. Second, those identified were contacted and asked to participate in a telephone interview. RESULTS: Of 1293 faculty identified by the residency directors, 769 participated in a research interview. Most of these teachers were full-time physician faculty, men, white, and based in departments of family medicine or psychiatry. Teaching was primarily conducted in hospitals, general outpatient clinics, and classrooms rather than alcohol and drug treatment programs. Less than 10% of the faculty performed clinical work in alcohol and drug treatment programs, and only 19% were certified addiction specialists. The respondents reported a definite need for additional development programs for themselves and other residency teaching faculty. CONCLUSIONS: We suggest a modest increase in the number of faculty who teach residents about substance abuse disorders, and the creation of additional faculty development programs.

Adult↗
PubMed1998

ID14 'Quadriga', a Beamline for Protein Crystallography at the ESRF.

The ESRF undulator beamline ID14 'Quadriga' is dedicated to monochromatic macromolecular crystallography. Using two undulators with 23 mm and 42 mm periods and a minimum gap of 16 mm installed on a high-beta section, it will provide high-brilliance X-ray beams at around 13.5 keV, as well as a wide tuneability between 6.8 and 40 keV. Based on the Troika concept, this beamline has four simultaneously operating experimental stations: three side stations, EH1, EH2 and EH3, using thin diamond crystals, and an end station, EH4, with a fast-scan double-crystal monochromator. Station EH3 has a kappa-diffractometer, and an off-line Weissenberg camera with a large 80 x 80 cm active area combined with a 2048 x 2048 CCD detector. During data collection the image plates are placed and removed by a robot located inside the hutch using a cassette system. After data collection the image plates are scanned with an off-line drum scanner. Station EH4 is designed for MAD applications, including Xe K-edge anomalous experiments, and is equipped with a 2048 x 2048 CCD detector on a pseudo 2theta arm. A common graphical user interface and a database will be available to cover all aspects of data collection, including strategy optimization. First results on the performance of the optics elements and initial crystallographic results are presented.

Journal Article↗
PubMed1998

Prenatal exposure to influenza and schizophrenia in Surinamese and Dutch Antillean immigrants to The Netherlands.

There is evidence of an increased incidence of schizophrenia in Afro-Caribbean immigrants to the UK and in Surinamese- and Dutch Antillean immigrants to The Netherlands. We tested the hypothesis that second-trimester exposure to the 1957 A2 influenza pandemic, which swept through the Caribbean in the same period as it affected Western Europe, contributes to this phenomenon. The dates of birth of immigrants, discharged from a Dutch psychiatric institute with a diagnosis of schizophrenia, were examined for any effect of the pandemic. Individuals who were in their second-trimester of fetal life at the peak of the pandemic were at no greater risk of developing schizophrenia than controls.

Adult↗
PubMed1998

Impact of transrenal aortic endograft placement on endovascular graft repair of abdominal aortic aneurysms.

PURPOSE: Successful endovascular repair of an abdominal aortic aneurysm (AAA) requires the creation of a hemostatic seal between the endograft and the underlying aortic wall. A short infrarenal aortic neck may be responsible for incomplete aneurysm exclusion and procedural failure. Sixteen patients who had an endograft positioned completely below the lowest renal artery and 37 patients in whom a porous portion of an endograft attachment system was deliberately placed across the renal arteries were studied to identify if endograft positioning could impact on the occurrence of incomplete aneurysm exclusion. METHODS: Fifty-three patients underwent aortic grafting constructed from a Palmaz balloon expandable stent and an expandable polytetrafluoroethylene (ePTFE) graft implanted in an aorto-ilio-femoral, femoral-femoral configuration. Arteriography, duplex ultrasonography and spiral CT scans were performed in each patient before and after endografting to evaluate for technical success, the presence of endoleaks, and renal artery perfusion. RESULTS: There was no statistically significant difference in patient demography, AAA size, or aortic neck length or diameter between patients who had their endografts placed below or across the renal arteries. However, significantly more proximal aortic endoleaks occurred in those patients with infrarenal endografts (P < or = .05). Median serum creatinine level before and after endografting was not significantly different between the 2 patient subgroups, with the exception of 2 patients who had inadvertent coverage of a single renal orifice by the endograft. Median blood pressure and the requirement for antihypertensive therapy remained the same after transrenal aortic stent grafting. Significant renal artery compromise did not occur after appropriately positioned transrenal stents as shown by means of angiography, CT scanning, and duplex ultrasound scan. Mean follow-up time was 10.3 months (range, 3 to 18 months). Patients who had significant renal artery stenosis (> or =50%) before aortic endografting did not show progression of renal artery stenosis after trans-renal endografting. Two patients with transrenal aortic stent grafts had inadvertent coverage of 1 renal artery by the endograft because of device malpositioning, which resulted in nondialysis dependent renal insufficiency. In addition, evidence of segmental renal artery infarction (<20% of the kidney), which did not result in an apparent change in renal function, was shown by means of follow-up CT scans in 2 patients with transrenal endografts. CONCLUSION: Transrenal aortic endograft fixation using a balloon expandable device in patients with AAAs can result in a significant reduction in the risk of proximal endoleaks. Absolute attention to precise device positioning, coupled with the use of detailed imaging techniques, should reduce the risk of inadvertent renal artery occlusion from malpositioning. Long-term follow-up is essential to determine if there will be late sequelae of transrenal fixation of endografts, which could adversely effect renal perfusion.

Aged↗
PubMed1998

Lower-pole caliceal stone clearance after shockwave lithotripsy, percutaneous nephrolithotomy, and flexible ureteroscopy: impact of radiographic spatial anatomy.

Spatial anatomy of the lower renal pole, as defined by the infundibulopelvic angle (LIP angle), infundibular length (IL), and infundibular width (IW), plays a significant role in the stone-free rate after shockwave lithotripsy. A wide LIP angle, a short IL, and a broad IW, individually or in combination, favor stone clearance, whereas a LIP <70 degrees, an IL >3 cm, or an IW < or =5 mm are individually unfavorable. When all three unfavorable factors or an unfavorable LIP and IL coexist, the post-SWL stone-free rate falls to 50% or less. Using these criteria, more than one fourth of our patients with a lower-pole calculus might have been better served by an initial percutaneous or perhaps ureteroscopic procedure, neither of which is significantly affected by the lower-pole spatial anatomy.

Adolescent↗