The transcriptional landscape of polyploid wheat.

The coordinated expression of highly related homoeologous genes in polyploid species underlies the phenotypes of many of the world's major crops. Here we combine extensive gene expression datasets to produce a comprehensive, genome-wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in homoeolog expression varies between tissues, with ~30% of wheat homoeologs showing nonbalanced expression. We found expression asymmetries along wheat chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar, and coding sequence variation, most often located in high-recombination distal ends of chromosomes. These transcriptionally dynamic genes potentially represent the first steps toward neo- or subfunctionalization of wheat homoeologs. Coexpression networks reveal extensive coordination of homoeologs throughout development and, alongside a detailed expression atlas, provide a framework to target candidate genes underpinning agronomic traits in wheat.

Plant programmed cell death from a chromatin point of view.

Programmed cell death (PCD) is a ubiquitous genetically regulated process consisting of the activation of finely controlled signalling pathways that lead to cellular suicide. PCD can be part of a developmental programme (dPCD) or be triggered by environmental conditions (ePCD). In plant cells, as in animal cells, extensive chromatin condensation and degradation of the nuclear DNA are among the most conspicuous features of cells undergoing PCD. Changes in chromatin condensation could either reflect the structural changes required for internucleosomal fragmentation of nuclear DNA or relate to large-scale chromatin rearrangements associated with a major transcriptional switch occurring during cell death. The aim of this review is to give an update on plant PCD processes from a chromatin point of view. The first part will be dedicated to chromatin conformational changes associated with cell death observed in various developmental and physiological conditions, whereas the second part will be devoted to histone dynamics and DNA modifications associated with critical changes in genome expression during the cell death process.

Obesity among adolescents in five Arab countries; relative to gender and age.

OBJECTIVE: To determine the prevalence of overweight and obesity among adolescents in five Arab countries, relative to age and sex. METHODS: A multistage stratified random sampling technique was used to select the secondary school students from five Arab countries (Kuwait, Libya, Palestine, Syria and United Arab Emirates). The total sample was 3302 (1584 males, 1718 females). Weight and height were measured, and body mass index was used to calculate the proportion of overweight and obesity based on the International Obesity Task Force standard (IOTF). RESULTS: Kuwaiti adolescents showed the highest prevalence of overweight and obesity among both males and females, compared to their counterparts in other countries. There was no trend in the proportion of overweight and obesity by age in any of the countries included in the study. CONCLUSION: Adolescent obesity has reached a critical level in the Arab countries. Therefore there is an urgent need to establish programs to prevent and control obesity among schoolchildren in these countries.

Objective: To determine the prevalence of overweight and obesity among adolescents in five Arab countries, relative to age and sex. Methods: A multistage stratified random sampling technique was used to select the secondary school students from five Arab countries (Kuwait, Libya, Palestine, Syria and United Arab Emirates). The total sample was 3302 (1584 males, 1718 females). Weight and height were measured, and body mass index was used to calculate the proportion of overweight and obesity based on the International Obesity Task Force standard (IOTF). Results: Kuwaiti adolescents showed the highest prevalence of overweight and obesity among both males and females, compared to their counterparts in other countries. There was no trend in the proportion of overweight and obesity by age in any of the countries included in the study. Conclusion: Adolescent obesity has reached a critical level in the Arab countries. Therefore there is an urgent need to establish programs to prevent and control obesity among schoolchildren in these countries.

The human VPAC1 receptor: three-dimensional model and mutagenesis of the N-terminal domain.

The human VPAC(1) receptor for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide belongs to the class II family of G-protein-coupled receptors with seven transmembrane segments. Like for all class II receptors, the extracellular N-terminal domain of the human VPAC(1) receptor plays a predominant role in peptide ligand recognition. To determine the three-dimensional structure of this N-terminal domain (residues 1-144), the Protein Data Bank (PDB) was screened for a homologous protein. A subdomain of yeast lipase B was found to have 27% sequence identity and 50% sequence homology with the N-terminal domain (8) of the VPAC(1) receptor together with a good alignment of the hydrophobic clusters. A model of the N-terminal domain of VPAC(1) receptor was thus constructed by homology. It indicated the presence of a putative signal sequence in the N-terminal extremity. Moreover, residues (Glu(36), Trp(67), Asp(68), Trp(73), and Gly(109)) which were shown to be crucial for VIP binding are gathered around a groove that is essentially negatively charged. New putatively important residues for VIP binding were suggested from the model analysis. Site-directed mutagenesis and stable transfection of mutants in CHO cells indicated that Pro(74), Pro(87), Phe(90), and Trp(110) are indeed important for VIP binding and activation of adenylyl cyclase activation. Combination of molecular modeling and directed mutagenesis provided the first partial three-dimensional structure of a VIP-binding domain, constituted of an electronegative groove with an outspanning tryptophan shell at one end, in the N-terminal extracellular region of the human VPAC(1) receptor.

Phase II trial of 7-day continuous 5-fluorouracil infusion in the treatment of advanced colorectal carcinoma.

Thirty-eight patients with advanced colorectal adenocarcinoma were entered on a phase II trial of 5-fluorouracil (5-FU) in continuous infusion, using a portable pump. Half of the patients had been pretreated (n = 19) and 16 of them had received intravenous bolus 5-FU alone or in combination. At the first cycle patients received continuous intravenous 5-FU at the dose of 650 mg/m2 per day for 7 consecutive days. Doses were escalated during the following cycles and adjusted according to the toxicities encountered in the previous cycle. Treatment was repeated every 3 weeks. A mean dose of 750 mg/m2/day (500-1,000) was administered for a mean number of 10 (1-25) cycles. We observed 1 complete response, 7 partial responses for a response rate of 21 +/- 13% (CI95%), 16 had stable disease (42%) and 14 a progression (37%). In 2 patients subsequently the residual tumors could be excised after chemotherapy. Median survival was 13.5 months. Toxicity was: grade 2 leukopenia in 1 patient (3%), mucositis grade 2-4 in 11 patients (29%), diarrhea grade 2-3 in 7 patients (18%), and hand and foot syndrome in 12 patients (31%). There was a correlation between the mean dose administered and the responses. However no clear correlation was found between toxicity and tumoral response for the first two cycles. These results confirm the limited efficacy of continuous intravenous 5-FU and its good tolerance in ambulatory patients.

[Lower anterior facial height excess at the end of orthodontic treatment: the value of genioplasty]. / Excès de hauteur faciale antérieure inférieure en fin de traitement orthodontique: intérêt de la génioplastie.

Despite successful orthodontic-orthopedic treatments, some patients present with lower face vertical excess, that causes labial incompetence. In order to treat that excess, and to restore normal balance between upper and lower face, the authors propose that functional genioplasty be carried out. Clinical and cephalometric criteria of vertical excess are describe, as well as the surgical technique and post-operative care. Several treated cases are presented.

A phase II study of cisplatin and continuous infusion of vindesine in metastatic head and neck squamous cell cancer.

The chemotherapeutic treatment of recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck (H & N) has a very dismal prognosis, with survival usually not exceeding 1 year. Reported objective response rates vary between 3% and 70%. This difference appears largely attributable to the heterogeneity of the patient populations included in most published Phase II studies in H & N cancer. They usually include together initially metastatic, recurrent, and post primary treatment metastatic disease patients. These patients respond differently to chemotherapy. Because of this situation, we decided to study a more homogeneous patient population consisting of metastatic patients only. Cisplatin (CDDP) and vindesine (VDS) are active agents in H & N SCC. As VDS has a cycle-specific activity, the therapeutic index may be increased if it is administered in a continuous infusion (CI) schedule. Thirty-three patients with metastatic H & N (69% biopsy proven) were treated with a combination regimen including CDDP (100 mg/m2) day 1 and VDS 0.6 to 1 mg/m2 for 96 hours of CI. Thirty-one patients were evaluable for response: five had a complete response (CR; 16%) and 11 had a partial response (PR; 36%) with an overall rate response of 52% (95% confidence limit: 33% to 70%). Median duration of CR was 6.4 months (3 to 19 months) and 4.4 months for PR (3 to 6 months). A decrease in the leukocytes was the main toxicity encountered with this regimen. This combination regimen containing CDDP and CI VDS was well tolerated and active in H & N SCC. The incorporation of an active vinca-alkaloid in neoadjuvant regimens should be considered.

96-hour continuous infusion of cis-platinum, 5-fluorouracil and bleomycin in recurrent or metastatic head and neck squamous cell carcinoma, unexpected anemia.

Cis-platinum, 5-fluorouracil and bleomycin are active agents in head and neck SCC. When given by continuous infusion (C.I.) lower toxicity and increased activity have been reported. A 4-day trial of triple C.I. including these reagents was conducted for recurrent and/or metastatic head and neck SCC. Cis-platinum 25 mg/m2/day, 5-FU 650 mg/m2/day and bleomycin 10 mg/m2/day were given for 4 days every 4 weeks. Twenty-nine patients were entered, 27 were evaluable for toxicity and 3 for response. The response rate was 30% (one CR and seven PR). Patient compliance was poor (one central and one peripheral i.v. line) and toxicity was acceptable except for the unexpected anemia; 48% of patients required red cell transfusion. One patient died of bleomycin-induced lung toxicity and minor renal toxicity related to parenteral hydration was observed in the first 16 patients. In conclusion, this combination is moderately active in recurrent and/or metastatic head and neck SCC. Patient compliance was poor and cumulative anemia was an unexpected toxic event. Further trials with this triple C.I. chemotherapy are not recommended for the alcoholic, undernourished, very advanced cancer patient population.

[Plasma androgens and testosterone binding globulin levels in hirsute women. Effects of dexamethasone and oestrogen-progestagen administration (author's transl)]. / Androgènes et capacité de liaison de la testostérone plasmatique chez la femme hirsute. Effets de l'administration de dexaméthasone et d'estroprogestatifs.

In a group of 19 women with idiopathic hirsutism plasma levels of testosterone binding globulin were significantly lowered, and plasma levels of total and unbound testosterone were significantly raised. After administration of dexamethasone or oestrogenprogestagen combination, the concentrations of free testosterone returned to the normal range for non hirsute women. This suggests that both the ovary and the adrenal cortex were responsible for the high plasma testosterone levels observed in these patients.