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P Bessette

Publications and source records attributed to P Bessette.

6 recordsLinked to original sources
PubMed2002

Gestational trophoblastic disease.

OBJECTIVE: To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT). OPTIONS: Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups. OUTCOMES: Improved mortality and morbidity. EVIDENCE: Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C). VALIDATION: These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

Antineoplastic Agents↗
PubMed1999

Mutations in the gene encoding the alpha-subunit of the Gs protein in molar pregnancy.

Molar pregnancy is a gestational trophoblastic disease associated with a trophoblastic proliferation and a protein synthesis alteration. It is characterized by the presence of hydatiform moles, which are fluid-filled cysts derived from the chorionic villi of the placenta. Recent studies have reported a reduced expression of several types of G proteins including Gsalpha in molar pregnancies suggesting alterations in G protein structure in hydatiform moles. To identify mutations that lead to Gsalpha deficiency, we isolated genomic DNA from hydatiform moles and used polymerase chain reaction to amplify all exons of the Gsalpha gene. Amplified Gsalpha gene fragments were analyzed by sequencing using the dideoxy chain termination method. Tissues obtained from three complete hydatiform moles and one partial hydatiform mole were examined. We have identified a heterozygous 8-bp deletion in exon 10 of the Gsalpha gene, in two complete hydatiform moles, that had evidence for a dysfunctional Gsalpha protein. This deletion produced a truncated protein. We have also identified a heterozygous polymorphism in exon 5 in two complete hydatiform moles, and a homozygous substitution (A-->G) in intron 5 of the Gsalpha gene in the other complete hydatiform mole; these two last types of mutations should not have any effects on protein activity.

Adult↗
PubMed1997

Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin.

The Escherichia coli periplasmic protein DsbC is active both in vivo and in vitro as a protein disulfide isomerase. For DsbC to attack incorrectly formed disulfide bonds in substrate proteins, its two active-site cysteines should be in the reduced form. Here we present evidence that, in wild-type cells, these two cysteines are reduced. Further, we show that a pathway involving the cytoplasmic proteins thioredoxin reductase and thioredoxin and the cytoplasmic membrane protein DsbD is responsible for the reduction of these cysteines. Thus, reducing potential is passed from cytoplasmic electron donors through the cytoplasmic membrane to DsbC. This pathway does not appear to utilize the cytoplasmic glutathione-glutaredoxin pathway. The redox state of the active-site cysteines of DsbC correlates quite closely with its ability to assist in the folding of proteins with multiple disulfide bonds. Analysis of the activity of mutant forms of DsbC in which either or both of these cysteines have been altered further supports the role of DsbC as a disulfide bond isomerase.

Aprotinin↗
PubMedDate not supplied

Expression of human placental G proteins during pregnancy.

OBJECTIVE: Regulatory guanine nucleotide-binding proteins (G proteins) play key roles in the stimulus-response coupling of many important biological systems. Recent studies from our laboratory suggest a functional role for many G proteins in the human placenta. However, the expression of these proteins has not yet been reported. Therefore, the aims of this investigation were to identify the expression of placental G protein alpha subunits in human placenta, and to study their level of variation during pregnancy. METHODS: Western and Northern blot analyses were performed on membrane protein and mRNA preparations, respectively, of human placentas from the first (7-11 weeks), second (16-19 weeks), and third (term) trimesters. RESULTS: The autoradiographs of both proteins and mRNA showed differential expression of placental G proteins during pregnancy. Thus, the relative levels of G alpha i2 and G alpha i3 subunits were highest during the first trimester, whereas no differences were observed between second-trimester and term placentas for both subunits. The levels of placental G alpha o and G alpha s subunits stayed relatively stable during pregnancy. CONCLUSION: The demonstration of human placental G alpha protein expression during pregnancy provides new insight into the components of the signal transduction machinery within trophoblast. However, the physiologic significance of the variations of placental G alpha i protein expression during pregnancy remains to be investigated.

Blotting, Northern↗
PubMedDate not supplied

Expression of G proteins in human placentae from molar pregnancies.

Hydatidiform mole is a conceptus, usually devoid of an intact fetus, with variable proliferation of trophoblast and altered placental protein synthesis, including high human chorionic gonadotropin (hCG) and low human placental lactogen (hPL) production. Little is known about the control of the production of these two placental proteins in molar pregnancies. Regulatory guanine 5'triphosphate (GTP)-binding proteins (G proteins) play key roles in the endocrine control of peptide production by the placenta. The present authors recently demonstrated that Gi2, Gi3 Go, and Gs alpha-subunits were expressed in normal human placenta throughout pregnancy. This study analysed the expression of placental G protein alpha-subunits in molar pregnancies. Western and Northern blot analyses were performed on membrane protein and total mRNA preparations of human placentae, respectively, from hydatidiform mole (n = 5) and normal pregnancies (n = 4). The levels of hPL and beta-hCG mRNAs were 60 and 237 per cent respectively, of those from normal placentae. The autoradiographs for G proteins and their mRNAs showed decreased expression in molar placentae in comparison with normal tissues. Specifically, G alpha i2, G alpha i3, G alpha o, and G alpha s levels reached 39, 4, 42, and 89 per cent, respectively, of those from normal placentae. In parallel with the protein levels, their mRNAs expression were 8, 3, 54 and 65 per cent of normal values for G alpha i2, G alpha i3, G alpha o, and G alpha s, respectively. The results demonstrate important changes in placental G protein expression in hydatidiform moles suggesting alterations in the signal transduction machinery within the molar trophoblast.

Autoradiography↗