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2.
Opt Express ; 24(6): 6542-52, 2016 Mar 21.
Article in English | MEDLINE | ID: mdl-27136844

ABSTRACT

In femtosecond laser machining, spatial beam shaping can be achieved with wavefront modulators. The wavefront modulator displays a pre-calculated phase mask that modulates the laser wavefront to generate a target intensity distribution in the processing plane. Due to the non-perfect optical response of wavefront modulators, the experimental distribution may significantly differ from the target, especially for continuous shapes. We propose an alternative phase mask calculation method that can be adapted to the phase modulator optical performance. From an adjustable number of Zernike polynomials according to this performance, a least square fitting algorithm numerically determines their coefficients to obtain the desired wavefront modulation. We illustrate the technique with an optically addressed liquid-crystal light valve to produce continuous intensity distributions matching a desired ablation profile, without the need of a wavefront sensor. The projection of the experimental laser distribution shows a 5% RMS error compared to the calculated one. Ablation of steel is achieved following user-defined micro-dimples and micro-grooves targets on mold surfaces. The profiles of the microgrooves and the injected polycarbonate closely match the target (RMS below 4%).

3.
Mol Ecol ; 23(9): 2313-25, 2014 May.
Article in English | MEDLINE | ID: mdl-24673681

ABSTRACT

Current population genetic models fail to cope with genetic differentiation for species with large, contiguous and heterogeneous distribution. We show that in such a case, genetic differentiation can be predicted at equilibrium by circuit theory, where conductance corresponds to abundance in species distribution models (SDMs). Circuit-SDM approach was used for the phylogeographic study of the lepidopteran cereal stemborer Busseola fuscaFüller (Noctuidae) across sub-Saharan Africa. Species abundance was surveyed across its distribution range. SDMs were optimized and selected by cross-validation. Relationship between observed matrices of genetic differentiation between individuals, and between matrices of resistance distance was assessed through Mantel tests and redundancy discriminant analyses (RDAs). A total of 628 individuals from 130 localities in 17 countries were genotyped at seven microsatellite loci. Six population clusters were found based on a Bayesian analysis. The eastern margin of Dahomey gap between East and West Africa was the main factor of genetic differentiation. The SDM projections at present, last interglacial and last glacial maximum periods were used for the estimation of circuit resistance between locations of genotyped individuals. For all periods of time, when using either all individuals or only East African individuals, partial Mantel r and RDA conditioning on geographic distance were found significant. Under future projections (year 2080), partial r and RDA significance were different. From this study, it is concluded that analytical solutions provided by circuit theory are useful for the evolutionary management of populations and for phylogeographic analysis when coalescence times are not accessible by approximate Bayesian simulations.


Subject(s)
Climate , Genetics, Population , Lepidoptera/genetics , Models, Genetic , Africa South of the Sahara , Animals , Bayes Theorem , Cluster Analysis , Genotype , Microsatellite Repeats , Phylogeography
4.
Public Health ; 126(1): 70-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22137096

ABSTRACT

OBJECTIVES: In September 2009, an increase in seasonal influenza vaccine adverse events (VAE), compared with reports for previous years, was detected among the French armed forces in the setting of an extended immunization campaign. This work presents the results of this investigation. STUDY DESIGN: VAE were surveyed among all French military personnel from 2008 to 2009 by Epidemiological Departments of the French Military Health Service. For each case, a notification form was completed, providing patient and clinical information. METHODS: Case definitions were derived from the French drug vigilance guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAE to the number of vaccine doses injected. RESULTS: Forty-seven seasonal influenza VAE were reported in continental France: 18 in 2008 and 29 in 2009. The annual reporting rate was higher in 2009 (31.6 vs 16.6 VAE per 100,000 injections, respectively). The highest monthly incidence was observed in September 2009 (60.8 events per 100,000 injections). Two other peaks were observed in February 2008 and March 2009. The incidence in September 2009 was not significantly different from the incidences in February 2008 and March 2009. It was observed that incidence peaks occurred during influenza epidemic periods. One serious neurological VAE was observed. CONCLUSIONS: The increase in seasonal influenza VAE in late 2009 mainly involved non-serious events, and could reflect stimulated reporting in the context of the A(H1N1)pdm09 pandemic. VAE reporting rates were highest during influenza epidemic periods, which could be explained by VAE being wrongly attributed to the vaccine when symptoms could reflect coincident background cases of viral infection.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/epidemiology , Influenza A Virus, H1N1 Subtype , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Military Personnel/statistics & numerical data , Adolescent , Adult , Female , France/epidemiology , Humans , Incidence , Male , Seasons , Vaccination , Young Adult
5.
Opt Express ; 19(10): 9035-43, 2011 May 09.
Article in English | MEDLINE | ID: mdl-21643157

ABSTRACT

The sensitivity of grating-coupled Surface Plasmon Polaritons (SPPs) on metallic surface has been exploited to investigate the correlation between ripples formation under ultrashort laser exposure and SPPs generation conditions. Systematic examination of coupling of single ultrashort laser pulse on gratings with appropriate periods ranging from 440 nm to 800 nm has been performed. Our approach reveals that a surface plasmon is excited only for an appropriate grating period, the nickel sample exhibits fine ripples pattern, evidencing the plasmonic nature of ripples generation. We propose a systematic investigation supported by a comprehensive study on the obtained modulation of such a coupling efficiency by means of a phenomenological Drude-Lorentz model which captures possible optical properties modification under femtosecond irradiation.

6.
Public Health ; 125(8): 494-500, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21767855

ABSTRACT

OBJECTIVES: An outbreak of novel A(H1N1) virus influenza, detected in Mexico in April 2009, spread worldwide in 9 weeks. The aim of this paper is to present the monitoring results of this influenza outbreak among French armed forces. STUDY DESIGN: The period of monitoring by the Military Influenza Surveillance System (MISS) was 9 months, from May 2009 to April 2010. METHODS: The main monitored events were acute respiratory infection (ARI), defined by oral temperature ≥38.5 °C and cough, and laboratory-confirmed influenza. Weekly incidence rates were calculated by relating cases to the number of servicepersons monitored. RESULTS: In continental France, the incidence of ARI increased from September 2009, with a weekly maxima of 401 cases per 100,000 in early December 2009 according to MISS. Estimations of the incidence of consultations which could be related to novel A(H1N1) influenza ranged from 48 to 57 cases per 100,000. CONCLUSIONS: The trends observed by MISS are compatible with French national estimations. The incidence of consultations which could be related to A(H1N1) influenza at the peak of the epidemic (194 cases per 100,000) was much lower than the national estimate (1321 cases per 100,000). This may be due to servicepersons who consulted in civilian facilities and were not monitored. Other explanations are the healthy worker effect and the younger age of the military population.


Subject(s)
Disease Outbreaks , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Population Surveillance , DNA Primers/chemistry , France , Humans , Incidence , Influenza, Human/virology , Military Medicine , Military Personnel/statistics & numerical data , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
7.
Med Trop (Mars) ; 71(5): 487-91, 2011 Oct.
Article in French | MEDLINE | ID: mdl-22235624

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate treatment adherence and its determinants in patients living with HIV followed up at the outpatient care and treatment center in Brazzaville, Congo. METHODS: This cross-sectional study included patients who attended the center from July to October 2009. Adherence was evaluated using a self-administered questionnaire, 5 distinct measurement tools, and global adherence index. Correlations between patient characteristics and adherence data were analyzed. RESULTS: A total of 214 patients were enrolled in the study. Mean patient age was 42 years. The female-to-male ratio was 2. There were 6 children. Most patients (92.5%) were receiving a first-line antiretroviral regimen; it consisted of a combination of zidovudine, lamivudine and nevirapine in 53.3% of cases. Adherence was estimated at 55.4-86.9% depending on the measurement tool. The global adherence index was significantly higher in patients who achieved their pre-defined life project (OR 4.33, p = 0.04) and in those who spoke lingala (OR 3.99, p = 0.01). After 6 months of antiretroviral therapy, mean weight gain was 4.8 kg; mean increase in CD4 was 104/mm3 (262 versus 158); and viral load was undetectable in 89.4% of patients. CONCLUSION: This study in Brazzaville (Congo) confirms that antiretroviral treatment adherence is satisfactory in sub-Saharan Africa. Adherence was mainly correlated with structural factors, e.g. language and life project, and with the patient friendliness of the regime. Most patients had favourable responses based on clinical, immunological, and virological criteria.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Medication Adherence/statistics & numerical data , Adult , Congo , Cross-Sectional Studies , Female , Humans , Male , Prospective Studies
8.
Opt Express ; 18(3): 2913-24, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-20174119

ABSTRACT

Precise nanostructuration of surface and the subsequent upgrades in material properties is a strong outcome of ultra fast laser irradiations. Material characteristics can be designed on mesoscopic scales, carrying new optical properties. We demonstrate in this work, the possibility of achieving material modifications using ultra short pulses, via polarization dependent structures generation, that can generate specific color patterns. These oriented nanostructures created on the metal surface, called ripples, are typically smaller than the laser wavelength and in the range of visible spectrum. In this way, a complex colorization process of the material, involving imprinting, calibration and reading, has been performed to associate a priori defined colors. This new method based on the control of the laser-driven nanostructure orientation allows cumulating high quantity of information in a minimal surface, proposing new applications for laser marking and new types of identifying codes.

9.
Arch Pediatr ; 26(6): 324-329, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31500922

ABSTRACT

AIMS: This study aimed to evaluate whether hospital-based home care was desired by the parents of children diagnosed with type 1 diabetes (T1D) under the age of 5 years and their general practitioners, and to identify the main expectations and obstacles to its implementation. METHODS: This descriptive bicentric study in France was performed between November 2016 and November 2017. Data were collected by interviewing 57 families of children diagnosed with diabetes before the age of 5 years and the corresponding 30 general practitioners. The primary endpoint was the families' or general practitioners' acceptance of home-based care after diagnosis. RESULTS: A high proportion of families and physicians (86% and 93%, respectively) expressed a wish for hospital-based home care, most of whom considered it essential (79% and 87%, respectively). Low-income families were less likely to accept this care pathway (P<0.001). The families' expectations regarding home care were help with social care, the management of emergencies, and return to school. The physicians' main request was improved interprofessional collaboration. CONCLUSION: Hospital-based home care seems to be an acceptable transition after conventional care for children just diagnosed with T1D. Multidisciplinary support, personalized social care, and access to welfare benefits may improve acceptance rates, especially among low-income families.


Subject(s)
Attitude of Health Personnel , Attitude to Health , Diabetes Mellitus, Type 1/therapy , General Practitioners , Home Care Services, Hospital-Based , Parents , Child , Child, Preschool , Cross-Sectional Studies , Diabetes Mellitus, Type 1/diagnosis , Female , France , Health Care Surveys , Humans , Infant , Male , Quality of Life
10.
Diagn Interv Imaging ; 100(4): 199-209, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30885592

ABSTRACT

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.


Subject(s)
Artificial Intelligence , Datasets as Topic , Breast Neoplasms/diagnostic imaging , Communication , Computer Security , Humans , Interprofessional Relations , Kidney Cortex/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Neoplasm Invasiveness/diagnostic imaging , Thyroid Cartilage/diagnostic imaging , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Tibial Meniscus Injuries/diagnostic imaging , Tomography, X-Ray Computed , Ultrasonography
11.
Arch Pediatr ; 14(1): 10-4, 2007 Jan.
Article in French | MEDLINE | ID: mdl-17118632

ABSTRACT

UNLABELLED: "Air swallowing" described as being part of functional gastrointestinal disorders in "Rome criteria" in 1999 is often misdiagnosed, particularly in non-mentally deficient children. AIMS: To recognize "air swallowing" child and to describe any progress according to the treatment. POPULATION AND METHODS: This retrospective study reports 13 cases of children without mental deficiency or neuromuscular disease. Clinical elements and precise histories are detailed and we have contacted consulting doctors or families for news. RESULTS: Ten boys and 3 girls, from 2,5 years to 10 years old, were referred for long lasting pain or abdominal distension. Numerous laboratory investigations were always normal. Diagnosis relied upon the observation of air swallowing and X-Rays views of gastric distension. Air swallowing was observed 7 times, 9 children had twitches and 3 language troubles. In 10 cases, X-rays showed gastric and colic distension. Three children have Chilaïditi syndrome. Favourable results followed in 12 cases after an average of 28 months of treatment. One case was lost for follow-up. Treatment was long, often disappointing and required the intervention of a psychiatrist, a paediatrician and (temporarily) a speech therapist. CONCLUSION: Pathological childhood aerophagia is often underdiagnosed and deserves to be better known by paediatricians, psychiatrists and surgeons. A late diagnosis leads to many negative results and causes anxiety. An early diagnosis should lead to a multidisciplinary care.


Subject(s)
Aerophagy/diagnosis , Aerophagy/therapy , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies
12.
Endocrinology ; 106(3): 718-23, 1980 Mar.
Article in English | MEDLINE | ID: mdl-7353539

ABSTRACT

Dopamine (DA) and DA agonists bind with high affinity to anterior pituitary receptors which mediate the inhibition of PRL release. Spiperone (SPIP), a DA antagonist, has also been successfully used to characterize pituitary DA receptors with a dissociation constant (Kd) of less than 1 nM. We studied the binding of SPIP to GH3D6 cells which secrete only PRL and GH. This clone was derived from a radiation-induced tumor of the rat anterior pituitary. Equilibrium binding of [3H]SPIP to living GH3 cells showed no high affinity receptors, but a low affinity (Kd = 0.83 microM) and saturable (0.06 fmol/cell) population of sites was observed. In addition, saturable binding with a similar affinity (Kd = 0.57 microM) was noted in broken GH3 cells. The interaction was completely reversible and temperature dependent. The concentration of various ligands required to compete for half of the [3H]SPIP binding to whole cells were: chlorpromazine, 0.17 microM; haloperidol, 0.68 microM; pimozide, 0.77 microM; d-butaclamol, 1.16 microM; 1-butaclamol, 1.30 microM; SPIP, 1.49 microM; bromergocryptine, 4.98 microM; apomorphine, 13.9 microM; and DA, 100 microM. The absence of a high affinity site in GH3 cells is consistent with the decreased effectiveness of various agonists and antagonists on PRL secretion. It is possible that the low affinity interactions observed in GH3 cells are normally present in the anterior pituitary and brain and do not simply represent an alteration of receptor affinity.


Subject(s)
Dopamine/pharmacology , Pituitary Neoplasms/metabolism , Prolactin/metabolism , Receptors, Dopamine/metabolism , Animals , Binding, Competitive , Cell Line , Cell Survival , Kinetics , Rats
13.
Endocrinology ; 107(4): 1022-6, 1980 Oct.
Article in English | MEDLINE | ID: mdl-6157521

ABSTRACT

The inhibitory regulation of PRL secretion by dopamine (DA) or the dopaminergic agonists bromergocryptine (CB-154) and apomorphine was studied in cultured GH3 cells, an established rat anterior pituitary cell line which produces both PRL and GH. The basal release of PRL from GH3 cells was unaffected when incubated for 6 h with DA concentrations as high as 10(-4) M. The inability of DA to suppress PRL secretion could not be explained by the catabolism of DA or the presence of unknown inhibitors (e.g. estradiol) in the fetal calf serum present in the incubation media. Apomorphine and CB-154 were only partially effective in suppressing PRL release at high concentrations of 10(-4) and 10(-5) M, respectively. Various concentrations of the dopaminergic antagonist d-butaclamol did not reverse the inhibitory action of 10(-5) M CB-154, while equal concentrations (10(-5) M) of both d- and l-butaclamol significantly suppressed PRL release. The greatly lowered responsiveness of GH3 cells to dopaminergic inhibition of PRL is suggestive of some impairment of DA receptors. This hypothesis is supported by radioligand binding studies in which high affinity dopaminergic binding sites are absent in the same cell line used in this study.


Subject(s)
Bromocriptine/pharmacology , Dopamine/pharmacology , Prolactin/metabolism , Animals , Apomorphine/pharmacology , Butaclamol/pharmacology , Cell Line , Clone Cells , Dose-Response Relationship, Drug , Mice , Pituitary Neoplasms
14.
J Clin Endocrinol Metab ; 79(6): 1716-22, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7989480

ABSTRACT

The purpose of the study was to evaluate the efficacy and safety of a sequential regimen of estrogen-progestin addition to GnRH agonist suppression in ovarian hyperandrogenism. Eight patients presenting with a polycystic ovary syndrome were treated with an sc implant of GnRH agonist every 4 weeks for 48 weeks. Starting at week 9, patients were replaced with 100 micrograms transdermal estradiol patches continuously and sequentially combined with 10 mg oral medroxyprogesterone acetate the last 2 weeks of each 4-week period. The rapid down-regulation of the pituitary-ovarian axis led to significant reduction of testosterone and androstenedione to 48.9% and 67.4% of baseline, respectively. During steroid replacement, testosterone and androstenedione continued to decrease gradually. The baseline hirsutism score (18.7 +/- 1.3) progressively fell to 9.7 +/- 2.0 at the end of treatment. The mean hair diameter was significantly reduced (0.097 +/- 0.004 vs. 0.081 +/- 0.005 mm). A withdrawal bleeding was obtained in 63.6% of the artificial cycles, but breakthrough bleeding occurred during 48% of the sequential replacements. The incidence of menopausal symptoms was low. There was a nonsignificant decrease in bone mineral content of the lumbar spine and the femoral neck but no trend in Ca2+/creatinine and OH-proline (OH-P)/creatinine ratios or in serum triglycerides and cholesterol fractions. There was a nonsignificant increase in hirsutism score in five patients followed up for 24 weeks after cessation of treatment, although there was a rapid return of hormones toward baseline and recurrence of irregular bleeding. Transdermal estradiol addition periodically combined with medroxyprogesterone acetate is effective in reducing hirsutism and is safe in minimizing side effects and bone loss. A regimen allowing a better bleeding control would make this approach a valuable alternative for prolonged or repeated palliative treatment of excessive hair growth and irregular bleeding in polycystic ovary syndrome.


Subject(s)
Estradiol/therapeutic use , Gonadotropin-Releasing Hormone/agonists , Hyperandrogenism/drug therapy , Medroxyprogesterone Acetate/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Administration, Cutaneous , Adolescent , Adult , Androstenedione/blood , Drug Implants , Estradiol/administration & dosage , Estradiol/adverse effects , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Hirsutism/drug therapy , Humans , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/adverse effects , Pilot Projects , Progesterone/blood , Testosterone/blood , Uterine Hemorrhage/chemically induced
15.
J Clin Endocrinol Metab ; 63(6): 1379-85, 1986 Dec.
Article in English | MEDLINE | ID: mdl-2946711

ABSTRACT

This study was designed to determine the effect of discontinuous administration of a LHRH agonist on pituitary-ovarian function in normal women. The LHRH agonist buserelin (200 micrograms/12 h or 400 micrograms/24 h) was given intranasally for four consecutive cycles for 14 or 21 days in 26 normally cycling women. Five milligrams of medroxyprogesterone acetate were given orally twice daily from days 15-21. There was a 7-day pause between each medication cycle. Blood samples were drawn every other day for RIA of LH, FSH, estradiol (E2), and progesterone (P). Serum FSH increased for only a few days at the beginning of each cycle, whereas sustained elevation of serum LH occurred during LHRH agonist administration. Serum E2 increased rapidly and remained elevated during the administration of buserelin. Serum P remained in the follicular phase range or increased briefly after the initiation of buserelin occasionally in the 14-day regimens. After discontinuation of buserelin, E2 fell rapidly, and uterine withdrawal bleeding occurred. During the pause, FSH increased progressively. The patterns of gonadotropin response to buserelin were similar in the four cycles. Based on measurement of the areas of the response curves, serum LH and E2 levels were higher during the administration of 200 micrograms/12 h compared to 400 micrograms/24 h buserelin. However, down-regulation of the pituitary-ovarian axis, as evaluated by the acute gonadotropin response to buserelin on day 14, was more pronounced with 200 micrograms/12 h than with 400 micrograms/24 h. Breakthrough bleeding occurred in the 14-day schedules, whereas withdrawal bleeding occurred during the pause in the 21-day schedules. The immediate cycles following buserelin administration were normal ovulatory cycles. Intermittent LHRH agonist administration for 21 days avoided constant down-regulation of the pituitary-ovarian axis and allowed regular uterine bleeding. Combined with an appropriate P complement, it could be a useful contraceptive approach.


Subject(s)
Buserelin/administration & dosage , Contraceptives, Oral, Combined/administration & dosage , Medroxyprogesterone/analogs & derivatives , Administration, Intranasal , Adult , Drug Administration Schedule , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Medroxyprogesterone/administration & dosage , Medroxyprogesterone Acetate , Menstrual Cycle/drug effects , Progesterone/blood
16.
J Clin Endocrinol Metab ; 81(1): 264-8, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8550762

ABSTRACT

Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn children. In contrast to CAH caused by 21 alpha-hydroxylase and 11 beta-hydroxylase deficiencies, which impairs steroid formation in the adrenal exclusively, 17 alpha-hydroxylase/17,20-lyase deficiency impairs steroid biosynthesis in the adrenals and gonads. The sequence of CYP17 gene was determined by direct sequencing of asymmetric PCR products in two French-Canadian 46,XY pseudohermaphrodite siblings suffering from combined 17 alpha-hydroxylase/17,20-lyase deficiency. The two patients are homozygous for the novel missense mutation R96W caused by a C to T transition converting codon Arg96 (CGG) into a Trp (TGG) in exon 1. The both parents are heterozygous for this missense mutation. We assessed the effect of the R96W mutation on 17 alpha-hydroxylase/17,20-lyase activity by analysis of mutant enzyme, generated by site-directed mutagenesis, expressed in COS-1 cells. The presence of R96W substitution almost completely abolished the activity of the mutant protein. The present findings provide a molecular explanation for the signs and symptoms of combined 17 alpha-hydroxylase/17,20-lyase deficiency in these two patients and provide useful information on the structure-activity relationships of the P450c17, enzyme.


Subject(s)
Aldehyde-Lyases/genetics , Cytochrome P-450 Enzyme System/genetics , Adolescent , Adult , Aldehyde-Lyases/deficiency , Base Sequence , Cytochrome P-450 Enzyme System/deficiency , Dehydroepiandrosterone/biosynthesis , Female , Humans , Male , Molecular Sequence Data , Mutation , Steroid 17-alpha-Hydroxylase
17.
Theor Appl Genet ; 104(4): 652-660, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12582670

ABSTRACT

Hybridisation between the annual diploid sunflower ( Helianthus annuus)and the perennial diploid species Helianthus mollis and Helianthus orgyalis was obtained by means of a normal crossing procedure or embryo rescue. Hybridisation success was low. All plants examined cytologically appeared to be diploid. However, the phenotypes of these diploids were not intermediate between the parents and, despite great variation, they resembled the female parent-type predominantly. Thirty five percent of plants issued from sunflower pollinated with perennial Helianthus had a phenotype resembling the female sunflower parent. On average, only 5% of the minimum number of expected RAPD and RFLP bands from male parents were recovered in plants produced from mature seeds after pollination of sunflower by H. mollis. More hybrids were found among plants obtained from embryo rescue, with an average of 25% of the male parent bands recovered per plant. Analysis of individual plants indicated the occurrence of various levels of hybridisation. There was a significant positive correlation between the number of phenotype traits related to hybrid status and the number of bands derived from the male parent. A single hybrid plant might possibly represent the product of a 'normal' hybridisation event. The mechanisms behind these unusual events and the consequences for the breeder are discussed.

18.
J Psychiatr Res ; 18(4): 513-39, 1984.
Article in English | MEDLINE | ID: mdl-6439854

ABSTRACT

Some basic concepts and trends which appear to be essential in the search for biological markers in mental disorders are discussed. Comments related to major psychosis and alcoholism are presented under three headings: (i) heterogeneity of disorders (ii) multifactoriality of disorders and (iii) mental disorders as genetically influenced disorders. Tentative classification and terminology of biological markers are given. Various types of phenotypic markers are discussed and alcoholism is taken as a model for a more detailed discussion of available putative phenotypic markers and of research strategies to be used, namely the pharmacological challenge in high risk subjects (e.g. ethanol and TRH challenge). Some highlights from the field of DNA markers are described, mainly the basic procedures which may be used to investigate genetic aspects of mental disorders by recombinant DNA technology.


Subject(s)
Alcoholism/genetics , Psychotic Disorders/genetics , Alcoholism/physiopathology , DNA, Recombinant , Ecology , Ethanol/metabolism , Genetic Linkage , Genetic Markers , Genotype , Humans , Phenotype , Polymorphism, Genetic , Prospective Studies , Risk , Thyrotropin-Releasing Hormone
19.
Urology ; 27(3): 221-8, 1986 Mar.
Article in English | MEDLINE | ID: mdl-3082058

ABSTRACT

A comparative study was done in 59 recently diagnosed Stage D2 prostatic cancer patients treated with either long-term GnRH-A (Buserelin) (N = 42) or with orchiectomy (N = 17) and followed up for three years. The suppressed limits of plasma testosterone and estradiol levels after eight-week follow-up as well as the objective clinical response and disease outcome were found to be similar with either treatment. Hot flushes and loss of libido were noticed in both groups throughout the follow-up period; however, there were no other side effects. Analysis of Stage D2 patients based on their time of death enables us to identify nonhormonal variables which, in the form of an aggressiveness score, correlated well with both clinical response and disease outcome. These data confirm that (1) Buserelin is an effective and safe alternative to orchiectomy in advanced prostatic cancer, and (2) in clinical studies a multifactor aggressiveness score is useful for analyzing clinical efficacy data. Prospective application of that score may enable predictability of patient response and influence patient management.


Subject(s)
Buserelin/therapeutic use , Orchiectomy , Prostatic Neoplasms/therapy , Buserelin/adverse effects , Climacteric , Follow-Up Studies , Humans , Libido/drug effects , Male , Neoplasm Staging , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Time Factors
20.
Fertil Steril ; 48(5): 775-82, 1987 Nov.
Article in English | MEDLINE | ID: mdl-2959569

ABSTRACT

Endometrial biopsies were performed in four groups of six or seven women treated for periods of 14 or 21 days with 200 micrograms twice daily or 400 micrograms once daily of intranasal Buserelin acetate. Five milligrams of medroxyprogesterone acetate (MPA) was taken orally twice daily on days 15 to 21. A medication-free week followed each treatment period. Between days 12 and 15 of the first treatment cycle, a proliferative endometrium was described in 16 out of 24 biopsies (66%). In 8 specimens (33%), early secretory changes were related to an early and/or short-lived rise in serum progesterone (P). At the end of the fourth treatment cycle, advanced maturation (days 23 to 28) was observed mainly in the 14-day schedules where serum estradiol (E2) was stimulated in or above the normal range of control cycles. Early to midluteal phase dating (days 16 to 22) was described mainly in the 21-day schedules. There was no P elevation in these groups. Five biopsies showing only proliferative tissue were associated with low levels of E2 mainly in the 400 micrograms/day group. The regimen capable of maintaining E2 in the low physiologic range (200 micrograms/12 hours X 21 days) was associated with incomplete secretory changes of the endometrium. A longer period of progestogen administration should produce a more complete maturation of the endometrium.


Subject(s)
Buserelin/therapeutic use , Endometrium/anatomy & histology , Medroxyprogesterone/analogs & derivatives , Adult , Biopsy , Buserelin/administration & dosage , Buserelin/pharmacology , Contraceptive Agents, Female , Endometrium/drug effects , Estradiol/blood , Female , Humans , Medroxyprogesterone/administration & dosage , Medroxyprogesterone/therapeutic use , Medroxyprogesterone Acetate , Menstrual Cycle , Progesterone/blood
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