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Biomedical subjects

M Antoine

Publications and source records attributed to M Antoine.

At least 19 recordsLinked to original sources
PubMed2006

Body composition in pregnancies of adolescents and mature women and the relationship to birth anthropometry.

OBJECTIVE: To investigate differences in body composition between adolescent girls and mature women during pregnancy and the relationship to newborn anthropometry. DESIGN: A prospective study. SETTING: The antenatal clinic at the University Hospital of the West Indies, Kingston, Jamaica. SUBJECTS: Four hundred and twenty-five women were invited to join the study. Three hundred and sixty-one women (84.9%) completed the study. INTERVENTIONS: Study participants were divided into two groups: adolescents and mature women, who were all less than 15 weeks pregnant and had no systemic illness at the time of entry into the study. A questionnaire was administered which retrieved information on demographics, age, marital status, menstrual history, parity, socio-economic status, medical history and smoking/drinking habits. Anthropometric measurements including weight, height, triceps, biceps, subscapular and suprailiac skinfolds, as well as blood pressure measurements and urine analysis were performed at the first antenatal visit and repeated at 15, 25 and 35 weeks gestation. Anthropometric measurements of the newborn were performed at birth. RESULTS: There were significant differences between anthropometry and skinfold thickness at the first antenatal visit between the adolescents and the mature women where the adolescents had lower measurements compared to the mature women. In the newborn anthropometry, the only significant difference seen was in the triceps skinfold thickness and the mid-upper arm circumference where the newborn of the adolescents had significantly smaller values (P=0.04; P=0.02, respectively). The percentage fat, fat mass and lean body mass were significantly lower in the adolescent compared to the mature women (P<0.0001), both at the first antenatal visit and at 35 weeks gestation. A greater gain was seen in these measurements throughout the pregnancy in the adolescents (P<0.0001). Linear regression analyses showed that the gain in lean body mass was the most important predictor of birth anthropometry. CONCLUSION: Body composition differs in pregnancy between adolescents and mature woman, and if adequate weight and lean body mass are attained, it impacts positively on birth size irrespective of age.

Adolescent↗
PubMed2006

Theoretical study of the reduction mechanism of sulfoxides by thiols.

Theoretical computations have been carried out to investigate the reaction mechanism of the sulfoxide reduction by thiols in solution. This reaction is a suitable model for enzymatic processes involving methionine sulfoxide reductases (Msrs). Recent investigations on the Msr mechanism have clearly shown that a sulfenic acid intermediate is formed on the catalytic cysteine of the active site concomitantly to the methionine product. In contrast, experimental studies for the reaction of a number of thiols and sulfoxides in solution did not observe sulfenic acid formation. Only, a disulfide was identified as the final product of the process. The present study has been carried out at the MP2/6-311+G(3d2f,2df,2p)//B3LYP/6-311G(d,p) level of theory. The solvent effect in DMSO has been incorporated using a discrete-continuum model. The calculations provide a basic mechanistic framework that allows discussion on the apparent discrepancy existing between experimental data in solution and in the enzymes. They show that, in the early steps of the process in solution, a sulfurane intermediate is formed the rate of which is limiting. Then, a proton transfer from a second thiol molecule to the sulfurane leads to the formation of either a sulfenic acid or a disulfide though the latter is much more stable than the former. If a sulfenic acid is formed in solution, it should react with a thiol molecule making its experimental detection difficult or even unfeasible.

Computer Simulation↗
PubMed2006

Fibroblast growth factor 16 and 18 are expressed in human cardiovascular tissues and induce on endothelial cells migration but not proliferation.

Endothelial cells line the blood vessel and precursor endothelial cells appear to have a pivotal effect on the organ formation of the heart, the embryonic development of the kidney, and the liver. Several growth factors including the fibroblast growth factors (FGF) seem to be involved in these processes. Ligands such as basic FGF produced and secreted by endothelial cells may also coordinate cellular migration, differentiation, and proliferation under pathological conditions including wound healing, tumorgenesis, and fibrogenesis in the adult. Recently we demonstrated the expression of two secreted FGFs, FGF16, and FGF18, in HUVEC and in rat aortic tissue. In the present report, we confirmed by RT-PCR analysis that FGF18 is wildly expressed in the cardiovascular tissue, while FGF16 showed a more restricted expression pattern. HUVEC clearly demonstrated chemotaxis towards FGF16 and FGF18. Both FGFs also enhanced cell migration in response to mechanical damage. However, recombinant FGF16 and FGF18 failed to induce endothelial cell proliferation or sprouting in a three-dimensional in vitro angiogenesis assay. Fgf18 expression was earlier reported in the liver, and we detected FGF18 expression in liver vascular and liver sinusoidal endothelial cells (LSECs), but not in hepatic parenchymal cells. Recombinant FGF18 stimulated DNA synthesis in primary hepatocytes, suggesting, that endothelial FGF18 might have a paracrine function in promoting growth of the parenchymal tissue. Interestingly, FGF2, which is mitogenic on endothelial cells and hepatocytes stimulates a sustained MAPK activation in both cell types, while FGF18 causes a short transient activation of the MAPK pathway in endothelial cells but a sustained activation in hepatocytes. Therefore, the difference in the time course of MAPK activation by the different FGFs appears to be the cause for the different cellular responses.

Animals↗
PubMed2006

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients.

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: review of a series of 271 patients with stage I and II breast cancer].

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy+/-systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N=37), DIP and medium or high SPF (DMH, N=76), ANEUP and low SPF (AL, N=24), ANEUP and medium or high SPF (AMH, N=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Breast Neoplasms↗
PubMed2005

Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: implications for its role in experimental biliary liver fibrogenesis.

Pleiotrophin (PTN) is a secretory heparin binding protein with various biological activities including mitogenesis, angiogenesis, and tissue repair after injury. Recent studies have shown that PTN is a strong mitogen of hepatocytes and involved in liver regeneration. In adult liver cells Ptn gene is mainly expressed by quiescent hepatic stellate cells (HSCs). Although we have been able to demonstrate mRNA and protein expression of the anaplastic lymphoma kinase-the receptor tyrosine kinase for PTN-on HSCs, PTN did not act as a mitogen of HSCs in contrast to hepatocytes. PTN immunoreactivity was markedly increased in experimental fibrogenesis by common bile duct ligation and observed in sinusoidal HSCs. In primary HSC cultures, Ptn transcription was significantly increased by PDGF-BB, and under hypoxic atmosphere. Mechanistically, hypoxia and PDGF mediated induction of PTN expression in sinusoidal HSCs may provide a strong mitogenic signal for hepatocytes to limit the damage to the parenchymal cells in biliary-type liver fibrogenesis.

Animals↗
PubMed2005

Identification of an unconventional nuclear localization signal in human ribosomal protein S2.

Ribosomal proteins must be imported into the nucleus after being synthesized in the cytoplasm. Since the rpS2 amino acid sequence does not contain a typical nuclear localization signal, we used deletion mutant analysis and rpS2-beta-galactosidase chimeric proteins to identify the nuclear targeting domains in rpS2. Nuclear rpS2 is strictly localized in the nucleoplasm and is not targeted to the nucleoli. Subcellular localization analysis of deletion mutants of rpS2-beta-galactosidase chimeras identified a central domain comprising 72 amino acids which is necessary and sufficient to target the chimeric beta-galactosidase to the nucleus. The nuclear targeting domain shares no significant similarity to already characterized nuclear localization signals in ribosomal proteins or other nuclear proteins. Although a Nup153 fragment containing the importinbeta binding site fused to VP22 blocks nuclear import of rpS2-beta-galactosidase fusion proteins, nuclear uptake of rpS2 could be mediated by several import receptors since it binds to importinalpha/beta and transportin.

Active Transport, Cell Nucleus↗
PubMed2005

Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer.

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Adult↗
PubMed2005

Expression pattern of fibroblast growth factors (FGFs), their receptors and antagonists in primary endothelial cells and vascular smooth muscle cells.

Fibroblast growth factors (FGFs) are important angiogenic growth factors. While basic FGF (FGF2) is well established as a potent inducer of angiogenesis much less is known about other FGFs possibly expressed by EC. We investigated the expression of all known FGFs, their main tyrosine kinase receptors and antagonists by RT-PCR analysis in human umbilical vascular endothelial cells (HUVECs) to obtain a complete expression profile of this important growth factor system in model endothelial cells (EC). In addition to FGFR1IIIc, which is considered as the major FGF receptor in EC, HUVECs express similar levels of FGFR3IIIc, detectable amounts of FGFR2IIIc and a new FGF receptor without an intracellular kinase domain (FGFR5). HUVECs express several secreted FGFs, including FGF5, 7, 8, 16 and 18 and two members of the fibroblast growth factor homologous factors (FHFs), not yet reported to be expressed in EC. The expression panel was compared with that obtained from human vascular smooth muscle cells (VSMCs) and human aortic tissue. Human umbilical artery smooth muscle cells (HUASMCs) and HUVECs express the identical FGF receptor and ligand panel implicating that both cell types act, according the FGF signals more as an entity than as individual cell types. Expression of Fgf1, 2, 7, 16 and 18 and the antagonists Sprouty 2,3 and 4 was demonstrated for all analysed cDNAs. The IIIc isoforms of FGFR1 and 2 and the novel FGFR5 were expressed in the aorta, but expression of the FGF receptor 3 was not detected in cDNAs derived from aortic tissue. In the VSMC of rat aortic tissue and in HUASM cultured cells we could demonstrate FGF18 immunoreactivity in the nucleus of the cells. The expression of several secreted FGFs by EC may focus the view more on their paracrine effects on neighbouring cells during tissue regeneration or tumor formation.

Amino Acid Sequence↗
PubMed2005

External quality assessment for molecular detection of Bordetella pertussis in European laboratories.

Although the PCR for the detection of Bordetella pertussis is routinely performed in diagnostic laboratories, no quality assessment program has so far been described. We report on the results obtained with two external quality assessment proficiency panels sent to European laboratories. The first proficiency panel contained a series of dilutions of three previously characterized B. pertussis clinical isolates and two negative controls. No false-positive results were reported by six laboratories providing seven data sets. The reported limits of detection of the three B. pertussis strains varied between 4 and 4,000, 9 and 9,000, and 3 and 30,000 CFU/ml, respectively. The second proficiency panel, composed of a series of dilutions of reference strains of B. pertussis, B. holmesii, B. hinzii, and B. bronchiseptica, as well as negative controls, was sent to nine laboratories. One laboratory reported a negative result for a sample and reported a B. parapertussis-positive sample to be positive for B. pertussis. By using the B. pertussis-specific target gene pertactin, one laboratory detected B. pertussis with 100% specificity. All other laboratories, which used IS481-based assays, reported positive results for the samples containing B. holmesii and B. bronchiseptica, species that have occasionally been recovered from human respiratory samples. These data show that the choice of the target gene is particularly critical for the species specificity of B. pertussis PCR assays.

Bordetella pertussis↗
PubMed2004

Upregulation of bronchioloalveolar carcinoma-derived C-X-C chemokines by tumor infiltrating inflammatory cells.

OBJECTIVE AND DESIGN: The presence of increased numbers of tumor-infiltrating neutrophils is associated with poorer outcome in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We evaluated the role of inflammatory environment on C-X-C chemokine tumor production. MATERIALS: Bronchoalveolar lavage from 31 consecutive patients with adenocarcinoma of the BAC subtype as well as tumor and normal pulmonary tissue samples. A549 BAC cell line. Peripheral blood mononuclear cells (PBMC), polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM). METHODS: Elisa measurements and immunohistochemical studies of ENA-78, IL-8, IL-1beta and TNF-alpha. RNA isolation, reverse transcription, and PCR amplification of ENA-78 and IL-8. RESULTS: C-X-C peptides were expressed by tumor cells of all the tumor specimens tested. ENA-78 and IL-8 were also expressed by AM. To better understand the regulation of the C-X-C production, BAC cell line was cultured alone or with inflammatory cells. PBMC upregulated both tumor ENA-78 and IL-8 mRNA expression and protein release whereas AM only upregulated ENA-78 mRNA expression and protein release; PMN had no effect. Anti-human IL-1beta antibodies (ab) inhibited the A549 ENA-78 and IL-8 production stimulated by PBMC-CM. Anti-human TNF-alpha ab inhibited A549 ENA-78 production stimulated by AM-CM. IL-1beta and TNF-alpha were expressed in vivo by inflammatory cells, although TNF-alpha was also expressed by tumor cells. CONCLUSIONS: This work emphasizes the role of the host inflammatory response in promoting tumor growth in vivo.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

[Preoperative concurrent radiation therapy and chemotherapy for operable bulky carcinomas of uterine cervix stages IB2, IIA, and IIB with proximal parametrial invasion].

PURPOSE: To evaluate preliminary results in terms of toxicity, local tumour control, and survival after preoperative concomitant chemoradiation for operable bulky cervical carcinomas. PATIENTS AND METHODS: Between December 1991 and October 2001, 42 patients (pts) with bulky cervical carcinomas stage IB2 (11 pts), IIA (15 pts), and IIB (16 pts) with 1/3 proximal parametrial invasion. Median age was 45 years (range: 24-75 years) and clinical median cervical tumour size was 5 cm (range: 4.1-8 cm). A clinical pelvic lymph node involvement has been observed in 10 pts. All patients underwent preoperative external beam pelvic radiation therapy (EBPRT) and concomitant chemotherapy during the first and the fourth radiation weeks combining 5-fluorouracil and cisplatin. The pelvic dose was 40.50 Gy over 4.5 weeks. EBPRT was followed by low-dose-rate uterovaginal brachytherapy with a total dose of 20 Gy in 17 pts. After a rest period of 5-6 weeks, all pts underwent class II modified radical hysterectomy with bilateral lymphadenectomy. Para-aortic lymphadenectomy was performed in eight pts without pathologic para-aortic lymph node involvement. Twenty-one of 25 pts who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy of 20 Gy. The median follow-up was 31 months (range: 3-123 months). RESULTS: Pathologic residual tumour or lymph node involvement was observed in 23 pts. Among the 22 pts with pathologic residual cervical tumour (<0.5 cm: nine pts; >or=0.5 to 1 cm: 10 pts), seven underwent preoperative EBRT followed by uterovaginal brachytherapy vs. 15 treated with preoperative EBRT alone (P = 0.23). Four pts had pathologic lymph node involvement, three pts had vaginal residual tumour, and four pts had pathologic parametrial invasion. The 2- and 5-year overall survival rates were 85% and 74%, respectively. The 2- and 5-year disease-free survival (DFS) rates were 80% and 71%, respectively. After multivariate analysis, the pathologic residual cervical tumour size was the single independent factor decreasing the probability of DFS (P = 0.0054). The 5-year local control rate and metastatic failure rate were 90% and 83.5%, respectively. Haematological effects were moderate. However, six pts had grade 3 acute intestinal toxicity. Four severe late complications requiring surgical intervention were observed (one small bowel complication, three ureteral complications). CONCLUSION: Primary concomitant chemoradiation followed surgery for bulky operable stage I-II cervical carcinomas can be employed with acceptable toxicity. However, systematic preoperative uterovaginal brachytherapy should increase local tumour control.

Adult↗
PubMed2004

Hypernatraemic dehydration in Jamaican breastfed neonates: a 12-year review in a baby-friendly hospital.

A 12-year retrospective review of neonates admitted with hypernatraemic dehydration to the neonatal unit of the University Hospital of the West Indies was conducted between 1 January 1990 and 31 December 2001. Twenty-four infants fulfilled the criteria for hypernatraemic dehydration. Nineteen (79%) women were either nulliparous or primiparous with a mean (SD) age of 26.9 (4.4) yrs. Modal length of hospital stay for mothers was 24 hrs. Twenty (83.3%) infants were exclusively breastfed. Mean (SD) age at presentation was 7.4 (3.8) days. Mean (SD) percentage weight loss between birth and presentation was 18.9% (6.3). Mean (SD) serum sodium at presentation was 164.8 (13.9) mmol/L. Babies visited at home by nurses had a lower mean serum sodium, were less dehydrated and were significantly less acidiotic. Their mean (SD) length of hospital stay was also significantly less [4.2 (1.4) days] than those who were not visited [7.9 (3.8) days] (p < 0.05). Complications occurred in 19 (79%) of infants and included renal failure (19, 79%), seizures (3, 13%) and intraventricular haemorrhage (1, 4%), and one died (4%). Hypernatraemic dehydration is an uncommon complication of failure to establish breastfeeding but is associated with severe morbidity and mortality. Education programmes are needed to increase awareness amongst health-care workers and mothers in order to prevent the problem.

Acidosis↗
PubMed2003

[Sentinel lymph node biopsy in breast cancer: technical aspects and results].

Sentinel lymph node biopsy for breast cancer has been introduced in the mid-1990s and it has now been performed on thousands of patients. Although this procedure has not been validated by randomised clinical trials, it has been rapidly adopted around the world by surgical specialists in clinical practice as a diagnostic procedure instead of the axillary lymph node dissection. The critical issue in sentinel lymph node biopsy is the false negative results which could expose the patients to axillary recurrence and lead to understaging and incorrect adjuvant therapy decisions. The current problem is to perfect the procedure for an optimal use in routine reducing this risk of false negative results. This false negative rate declines sharply when the technique is performed in selected patients by experienced surgeons using a combined detection. In this article, we review the technical aspects and results of the sentinel lymph node biopsy in breast cancer and discuss the recommendations for the optimal clinical practice.

Breast Neoplasms↗