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Biomedical subjects

D Bourgeois

Publications and source records attributed to D Bourgeois.

At least 19 recordsLinked to original sources
PubMed2000

Towards automated Laue data processing: application to the choice of optimal X-ray spectrum.

Laue data reduction has now reached a level of sophistication that allows nearly automated processing to be performed. The software described enables complete reduction of the data with essentially no user intervention, making Laue processing almost as straightforward as monochromatic data processing. Interactive work is limited to the indexing of only one Laue pattern. More importantly, it is shown that the data quality is substantially enhanced when soft-limited predictions are used. Further improvement obtained by taking advantage of the structure-factor amplitudes from a known closely related structure is described. To determine the most suitable type of insertion device to be used for time-resolved Laue crystallography, the technique described was applied to Laue data sets collected from photoactive yellow protein under identical conditions but with three different insertion devices: a wiggler, a broad-bandpass undulator and a single-line undulator. Although the optimal choice may ultimately be dictated by sample parameters (such as mosaic spread) and by the type of experiment (repeatable or non-repeatable reactions), the results here show that the use of single-line undulators will generally yield by far the best compromise between data quality, acquisition time and radiation damage.

Bacterial Proteins↗
PubMed1999

Does the reduction of c heme trigger the conformational change of crystalline nitrite reductase?

The structures of nitrite reductase from Paracoccus denitrificans GB17 (NiR-Pd) and Pseudomonas aeruginosa (NiR-Pa) have been described for the oxidized and reduced state (Fülöp, V., Moir, J. W. B., Ferguson, S. J., and Hajdu, J. (1995) Cell 81, 369-377; Nurizzo, D., Silvestrini, M. C., Mathieu, M., Cutruzzolà, F., Bourgeois, D., Fülöp, V., Hajdu, J., Brunori, M., Tegoni, M., and Cambillau, C. (1997) Structure 5, 1157-1171; Nurizzo, D., Cutruzzolà, F., Arese, M., Bourgeois, D., Brunori, M., Cambillau, C. , and Tegoni, M. (1998) Biochemistry 37, 13987-13996). Major conformational rearrangements are observed in the extreme states although they are more substantial in NiR-Pd. The four structures differ significantly in the c heme domains. Upon reduction, a His17/Met106 heme-ligand switch is observed in NiR-Pd together with concerted movements of the Tyr in the distal site of the d1 heme (Tyr10 in NiR-Pa, Tyr25 in NiR-Pd) and of a loop of the c heme domain (56-62 in NiR-Pa, 99-116 in NiR-Pd). Whether the reduction of the c heme, which undergoes the major rearrangements, is the trigger of these movements is the question addressed by our study. This conformational reorganization is not observed in the partially reduced species, in which the c heme is partially or largely (15-90%) reduced but the d1 heme is still oxidized. These results suggest that the d1 heme reduction is likely to be responsible of the movements. We speculate about the mechanistic explanation as to why the opening of the d1 heme distal pocket only occurs upon electron transfer to the d1 heme itself, to allow binding of the physiological substrate NO2- exclusively to the reduced metal center.

Ascorbic Acid↗
PubMed1999

New processing tools for weak and/or spatially overlapped macromolecular diffraction patterns.

Tools originally developed for the treatment of weak and/or spatially overlapped time-resolved Laue patterns were extended to improve the processing of difficult monochromatic data sets. The integration program PrOW allows deconvolution of spatially overlapped spots which are usually rejected by standard packages. By using dynamically adjusted profile-fitting areas, a carefully built library of reference spots and interpolation of reference profiles, this program also provides a more accurate evaluation of weak spots. In addition, by using Wilson statistics, it allows rejection of non-redundant strong outliers such as zingers, which otherwise may badly corrupt the data. A weighting method for optimizing structure-factor amplitude differences, based on Bayesian statistics and originally applied to low signal-to-noise ratio time-resolved Laue data, is also shown to significantly improve other types of subtle amplitude differences, such as anomalous differences.

Computer Graphics↗
PubMed1999

Noma: public health problem in Senegal and epidemilogical surveillance.

Noma or cancrum oris is currently a real public health problem for developing countries. In Senegal, awareness of the disease has led the country to be included in the noma programme initiated by the WHO as early as 1994. The objectives are to evaluate the incidence of necrotizing ulcerative gingivitis (NUG) among children, to evaluate the prevalence of noma and infantile diseases, and to promote prevention strategies among vulnerable populations. Data processing was carried out in two phases: manual processing consisted of checking the questionnaires by nurses, and computer processing started as early as the first collection of data. Noma occurs owing to fever and similar cases. Successfully fighting against malnutrition would allow us to reduce the noma rate.

Adolescent↗
PubMed1999

Caries prevalence in 12-year-old schoolchildren in Senegal in 1989 and 1994.

Senegal, in middlewest Africa, has an estimated area of 197,000 km2 with a population of about 8.3 million of whom 45 per cent are less than 14-years of age. Apart from densely populated areas around the capital, Dakar, and other large towns, the population is scattered sparsely in rural areas. In the absence of any recent and representative oral health data, two cross-sectional studies on caries prevalence were conducted in 1989 and 1994 respectively to assess and compare the caries status among 12-year-old schoolchildren living in the urban and rural areas of Senegal. The results of the study are presented in this paper.

Child↗
PubMed1999

[Conservative treatment of multifocal breast cancer: a comparative study].

Conservative treatment of multifocal breast cancer is still very controversial. This retrospective study concerns 56 patients with stage I or II multifocal breast cancer who underwent conservative treatment at the Institut Curie from January 1983 to December 1989. These patients (group 1) were matched with 132 patients with multifocal lesions treated by mastectomy (group 2). Surgical treatment consisted of a single wide lumpectomy followed by external radiotherapy. Adjuvant systemic therapy and regional nodal irradiation were administered as indicated by current protocols. The actuarial 5-year overall survival rate was 94% 6 in group 1, and 90% 6 in group 2 (NS). The actuarial 5-year ipsilateral breast recurrence rate was 11% 8 in group 1, and 11% 5 in group 2 (NS). In group 1 patients, the ipsilateral breast recurrence rate was related neither to type of multifocality nor to presence of intra ductal breast carcinoma, nodal status, tumor margins, radiotherapy boost, or distance between tumors. Consequently, conservative treatment of multifocal breast cancers which can be completely removed by a single lumpectomy seems, when technically feasible, an alternative to mastectomy.

Adult↗
PubMed1999

Oral health status in 65-74 years old adults in France, 1995.

BACKGROUND: A study was carried out to assess the oral health status of the non-institutionalized population aged 65-74 years and living in the Rhône-Alpes region, France, in 1995. METHODS: The representative sample was composed of 603 subjects comprised of 41.5% of men of which 24.5% lived in rural areas--i.e. less than 2,000 inhabitants--and 75.5% of urban areas. The quota sample used was stratified by socio-economic status, residence and gender. Oral health was defined by dentate status, D (Decayed), M (Missing), F (Filled) components and DMFT components. Carious lesions, fillings, missing teeth were recorded using the World Health Organization criteria. An indicator of treatment need--the ratio of decayed teeth over decayed and filled teeth--D/D+F was used. RESULTS: The DMFT index at 65-74 years for the French population was 23.3 +/- 4.0. The dental condition of the study group in the Rhônes-Alpes region of France appears satisfactory considering the low percentage of untreated decayed teeth at 65-74 years old (17.4%) and the low rate of edentate people (16.3%). Gender, location and socio-economic variables in relation to the dental status were discussed. CONCLUSION: The relatively good oral health status of the senior citizens and the low rate of need for treatment of dental decay together with the level of oral care available provided a solid base for further development of a qualitative national dental care system.

Aged↗
PubMed1999

[Identification of sentinel lymph node in breast cancer: experience from the Institut Curie].

Sentinel lymph node (SN) biopsy is a recently developed, minimally invasive technique for staging the axilla in breast cancer. This new procedure of selective lymphadenectomy has been the subject of several studies, but there is not currently a consensus of opinion to define which is the best method of identification. At the Institut Curie since 1996, we have been using the Patent blue dye. The current series present the result of 122 patients with T1, T2, N0 or N1a breast cancer consecutively operated between december 1997 and august 1998. Sentinel nodes were identified in 107 out of 122 (87.7%) and accurately predicted axillary nodal status in 104 out of 107 (97.1%) cases. Three out of 35 node positive patients would have been missed with sentinel node biopsy alone, for a false negative rate of 8.5%. In all 3 cases, one lymph node presented with a micrometastases. In 15 cases out of 35 with metastatic axillary nodes, the only positive node was the SN (43%). The encouraging results of this study shows that it is possible to identify, in a large number of cases, the sentinel node by means of Patent blue dye only. This article detailed the technique used and reviews the literature concerning other methods of identification.

Adult↗
PubMed1998

Static Laue diffraction studies on acetylcholinesterase.

Acetylcholinesterase (AChE) is one of nature's fastest enzymes, despite the fact that its three-dimensional structure reveals its active site to be deeply sequestered within the molecule. This raises questions with respect to traffic of substrate to, and products from, the active site, which may be investigated by time-resolved crystallography. In order to address one aspect of the feasibility of performing time-resolved studies on AChE, a data set has been collected using the Laue technique on a trigonal crystal of Torpedo californica AChE soaked with the reversible inhibitor edrophonium, using a total X-ray exposure time of 24 ms. Electron-density maps obtained from the Laue data, which are of surprisingly good quality compared with similar maps from monochromatic data, show essentially the same features. They clearly reveal the bound ligand, as well as a structural change in the conformation of the active-site Ser200 induced upon binding.

Acetylcholine↗
PubMed1998

Conformational changes occurring upon reduction and NO binding in nitrite reductase from Pseudomonas aeruginosa.

Nitrite reductase (NiR) from Pseudomonas aeruginosa (EC 1.9.3.2) (NiR-Pa) is a soluble enzyme catalyzing the reduction of nitrite (NO2-) to nitric oxide (NO). The enzyme is a 120 kDa homodimer, in which each monomer carries one c and one d1 heme. The oxidized and reduced forms of NiR from Paracoccus denitrificans GB17 (previously called Thiosphaera pantotropha) (NiR-Pd) have been described [Fülop, V., et al. (1995) Cell 81, 369-377; Williams, P. A., et al. (1997) Nature 389, 406-412], and we recently reported on the structure of oxidized NiR-Pa at 2.15 A [Nurizzo, D., et al. (1997) Structure 5, 1157-1171]. Although the domains carrying the d1 heme are almost identical in both NiR-Pa and NiR-Pd oxidized and reduced structures, the c heme domains show a different pattern of c heme coordination, depending on the species and the redox state. The sixth d1 heme ligand in oxidized NiR-Pd was found to be Tyr25, whereas in NiR-Pa, the homologuous Tyr10 does not interact directly with Fe3+, but via a hydroxide ion. Furthermore, upon reduction, the axial ligand of the c heme of NiR-Pd changes from His17 to Met108. Finally, in the oxidized NiR-Pa structure, the N-terminal stretch of residues (1-29) of one monomer interacts with the other monomer (domain swapping), which does not occur in NiR-Pd. Here the structure of reduced NiR-Pa is described both in the unbound form and with the physiological product, NO, bound at the d1 heme active site. Although both structures are similar to that of reduced NiR-Pd, significant differences with respect to oxidized NiR-Pd were observed in two regions: (i) a loop in the c heme domain (residues 56-62) is shifted 6 A away and (ii) the hydroxide ion, which is the sixth coordination ligand of the heme, is removed upon reduction and NO binding and the Tyr10 side chain rotates away from the position adopted in the oxidized form. The conformational changes observed in NiR-Pa as the result of reduction are less extensive than those occurring in NiR-Pd. Starting with oxidized structures that differ in many respects, the two enzymes converge, yielding reduced conformations which are very similar to each other, which indicates that the conformational changes involved in catalysis are considerably diverse.

Crystallization↗
PubMed1998

Energy transduction on the nanosecond time scale: early structural events in a xanthopsin photocycle.

Photoactive yellow protein (PYP) is a member of the xanthopsin family of eubacterial blue-light photoreceptors. On absorption of light, PYP enters a photocycle that ultimately transduces the energy contained in a light signal into an altered biological response. Nanosecond time-resolved x-ray crystallography was used to determine the structure of the short-lived, red-shifted, intermediate state denoted [pR], which develops within 1 nanosecond after photoelectronic excitation of the chromophore of PYP by absorption of light. The resulting structural model demonstrates that the [pR] state possesses the cis conformation of the 4-hydroxyl cinnamic thioester chromophore, and that the process of trans to cis isomerization is accompanied by the specific formation of new hydrogen bonds that replace those broken upon excitation of the chromophore. Regions of flexibility that compose the chromophore-binding pocket serve to lower the activation energy barrier between the dark state, denoted pG, and [pR], and help initiate entrance into the photocycle. Direct structural evidence is provided for the initial processes of transduction of light energy, which ultimately translate into a physiological signal.

Bacterial Proteins↗
PubMed1998

Conservative treatment of lower pole breast cancers by bilateral mammoplasty and radiotherapy.

AIMS: This series analyses the results of conservative surgery for large lower pole breast cancers by lumpectomy associated with a bilateral remodelling mammoplasty, in order to avoid residual deformities. METHODS: This retrospective study concerns 50 patients with a lower pole breast cancer treated between 1986 and 1996 by lumpectomy, mammoplasty and irradiation. The contralateral breast was immediately made symmetrical in all cases. The mean tumour size was 32.5 mm. RESULTS: The mean weight of the lumpectomy specimen was 270 g. Resection margins were tumour-free in 90% of cases. The main complication observed was delayed healing, thus postponing post-operative treatment in 6.5% of cases. The median follow-up was 48 months. The 5-year actuarial ipsilateral local recurrence rate was 7% and 5-year actuarial metastasis-free and overall survival rates were 81 and 97%, respectively. Cosmesis was satisfactory in 85% of patients. We observed better results when radiotherapy was performed after rather than prior to surgery (92 vs. 67%: NS). CONCLUSIONS: Performing a bilateral mammoplasty at the time of initial surgery for large breast cancers situated in the lower quadrants of the breast facilitates larger lumpectomies with good cosmetic results.

Adult↗
PubMed1998

WHO Global Oral Data Bank, 1986-96: an overview of oral health surveys at 12 years of age.

The global oral health situation of 12-year-old children--decayed, missing, filled teeth (DMFT) index and the percentage of population affected--is described in this article using the latest representative studies for 80 countries included in the WHO Global Oral Data Bank (GODB) between 1986 and 1996. The quantity of information varied considerably: 68% of developed market economies had at least one national data set, compared with 38% of developing countries and 36% of economies in transition. By WHO region, the proportions were as follows: Eastern Mediterranean, 55%; European, 50%; Western Pacific, 48%; African, 39%; South-East Asia, 30%; and the Americas, 26%. Globally, the weighted DMFT index for all data in the GODB is < 3.0%, the WHO/Fédération Dentaire Internationale goal for the year 2000. For the data reviewed in this article, achievement and nonachievement of this goal are discussed, as is the variation in DMFT means and proportions of children affected for various country groupings. There are difficulties in obtaining recent data for many countries, but the article emphasizes the need to maintain and develop the GODB to facilitate the compilation of valid, reliable and comparable data on oral health.

Child↗
PubMed1998

[Indications for diagnosing nonpalpable breast lesions].

The increasingly widespread use of mammographic screening for breast cancer has induced a considerable increase in the number of surgical biopsies. Fine-needle aspiration and microbiopsies can allow to reduce this number. 1) In patients with nodular densities of benign or indeterminate appearance, a negative fine-needle aspiration indicates that no further investigations are needed. In contrast, complete surgical excision is indicated in cases of stellate images. 2) In patients with potentially malignant microcalcifications, fine-needle aspiration is to little value, and microbiopsies should be performed. Indeterminate (type II or III) calcifications are the best indication, since negative microbiopsies may obviate the need for lumpectomy, if the negative predictive value of microbiopsies is sufficiently high in this indication. Focal suspicious microcalcifications (type IV or V) should be removed surgically for both diagnostic and therapeutic purposes. Type IV or V microcalcifications involving a large area of the breast can be investigated by initial microbiopsy; a positive result allows to recommend immediate mastectomy without prior lumpectomy. Fine-needle aspiration and microbiopsies should be performed as part of a multidisciplinary diagnostic strategy involving radiologists, surgeons, cytopathologists, and pathologists. This approach is the only means of improving the management of non palpable mammographic lesions and of reducing the number of unnecessary operation.

Biopsy↗
PubMed1998

Prevalence of caries and edentulousness among 65-74-year-olds in Europe.

Reviewed in this article are epidemiological studies included in the WHO Global Oral Data Bank for noninstitutionalized European adults aged 65-74 years for the period 1986-96. Edentulous percentages, decayed, missing, filled teeth (DMFT) index, and data on the mean number of teeth are presented. At least one representative study had been carried out in 48% of the countries, with the quantity of information from countries with developed market economies being similar to that from countries with economies in transition. The proportion of 65-74-year-olds who were edentulous varied from 12.8% to 69.6%, the mean number of teeth ranged from 15.1 to 3.8, and the DMFT index from 22.2 to 30.2. The observed disparities in the oral health status among older European adults suggest that it may be possible to develop and implement oral health policies that take into account geographical and socioeconomic differences in populations.

Aged↗
PubMed1997

N-terminal arm exchange is observed in the 2.15 A crystal structure of oxidized nitrite reductase from Pseudomonas aeruginosa.

BACKGROUND: Nitrite reductase from Pseudomonas aeruginosa (NiR-Pa) is a dimer consisting of two identical 60 kDa subunits, each of which contains one c and one d1 heme group. This enzyme, a soluble component of the electron-transfer chain that uses nitrate as a source of energy, can be induced by the addition of nitrate to the bacterial growth medium. NiR-Pa catalyzes the reduction of nitrite (NO2-) to nitric oxide (NO); in vitro, both cytochrome c551 and azurin are efficient electron donors in this reaction. NiR is a key denitrification enzyme, which controls the rate of the production of toxic nitric oxide (NO) and ultimately regulates the release of NO into the atmosphere. RESULTS: The structure of the orthorhombic form (P2(1)2(1)2) of oxidized NiR-Pa was solved at 2.15 A resolution, using molecular replacement with the coordinates of the NiR from Thiosphaera pantotropha (NiR-Tp) as the starting model. Although the d1-heme domains are almost identical in both enzyme structures, the c domain of NiR-Pa is more like the classical class I cytochrome-c fold because it has His51 and Met88 as heme ligands, instead of His17 and His69 present in NiR-Tp. In addition, the methionine-bearing loop, which was displaced by His17 of the NiR-Tp N-terminal segment, is back to normal in our structure. The N-terminal residues (5/6-30) of NiR-Pa and NiR-Tp have little sequence identity. In Nir-Pa, this N-terminal segment of one monomer crosses the dimer interface and wraps itself around the other monomer. Tyr10 of this segment is hydrogen bonded to an hydroxide ion--the sixth ligand of the d1-heme Fe, whereas the equivalent residue in NiR-Tp, Tyr25, is directly bound to the Fe. CONCLUSIONS: Two ligands of hemes c and d1 differ between the two known NiR structures, which accounts for the fact that they have quite different spectroscopic and kinetic features. The unexpected domain-crossing by the N-terminal segment of NiR-Pa is comparable to that of 'domain swapping' or 'arm exchange' previously observed in other systems and may explain the observed cooperativity between monomers of dimeric NiR-Pa. In spite of having similar sequence and fold, the different kinetic behaviour and the spectral features of NiR-Pa and NiR-Tp are tuned by the N-terminal stretch of residues. A further example of this may come from another NiR, from Pseudomonas stutzeri, which has an N terminus very different from that of the two above mentioned NiRs.

Amino Acid Sequence↗
PubMed1997

[Breast cancers with central localization: conservative treatment by tumorectomy with ablation of the areolar plaque].

OBJECTIVES: In breast cancer, retroareolar tumors are observed in 5 to 20% of cases; mammectomy is the conventional treatment. Conservative surgery was used in this series of 36 patients with retroareolar cancer situated less than 2 cm from the areola. PATIENTS AND METHODS: Tumorectomy with resection of the areolar plaque was followed by radiotherapy. Six patients had Paget's disease of the nipple, 64% were in classes T0 or T1 and 36% in T2. Chemotherapy or radiotherapy was given for tumor reduction prior to surgery in 8 patients. Wide tumorectomy with resection of the areolar plaque and gland remodeling was performed in all patients. Three plastic surgery techniques were used. Mean tumor size was 17.3 mm (8 to 33 mm). The areola was invaded in 16 patients (44%) and the derma or retroareolar ducts in 26 (72%). RESULTS: The mean distance between the tumor and skin surface was 3.8 mm. The section surface was in healthy tissue in 31 patients and 2 patients underwent subsequent surgery for mammectomy. All patients had either pre-operative (n = 4) or post-operative (n = 32) radio-therapy. Secondary reconstruction of the nipple was performed in 14 patients. CONCLUSION: Histology findings and esthetic results suggested that this conservative approach can be proposed when the tumor is located close to the areola, as confirmed by our series and results from other teams using the same technique.

Adult↗