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Biomedical subjects

G Noel

Publications and source records attributed to G Noel.

At least 19 recordsLinked to original sources
PubMed2006

Proton beam therapy for iris melanomas.

AIMS: To describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation. METHODS: Retrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume. RESULTS: A total of 21 patients were treated, median follow-up of 33 months (8-72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2-8 mm), the median ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma. CONCLUSIONS: Proton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.

Adolescent↗
PubMed2006

[Brain metastasis radiotherapy].

Brain metastases are an important cause of mortality and morbidity. The prognosis is poor with a median survival of less than one year in the majority of cases. From this review, whole-brain irradiation clearly appears as the standard treatment. However, its role could be discussed according to newer treatment modalities, radiosurgery or new chemotherapies. Post irradiation neurocognitive status remains insufficiently known.

Brain Neoplasms↗
PubMed2003

[Epstein-Barr virus associated central nervous system leiomyosarcoma occurring after renal transplantation: case report and review of the literature].

Central nervous system leiomyosarcomas are extremely rare, however, they became more frequent among immunodeficient patients, either in a patients infected with human immunodeficiency virus (HIV), or after organ transplantation. The data of the literature indicate that the infection by Epstein-Barr virus (EBV) plays a causal role in the development of these tumours but its precise role in the oncogenesis remains unresolved. We report a new case of EBV associated leiomyosarcoma of the left cavernous sinus occurring after renal transplantation. The epidemiological, clinical, pathological and therapeutic characteristics of these tumours are discussed.

Adult↗
PubMed2002

[Results of proton beam irradiation for treatment of choroidal melanoma].

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.

Adolescent↗
PubMed2001

Stress hormone secretion and gut signal transducer (STAT) proteins after burn injury in rats.

A burn injury triggers traumatic reactions characteristics of a stress. Here we investigated the early responses of prolactin (PRL), corticosterone (CS), and signal transducer and activator of transcription 5 (STAT5) in male Sprague-Dawley rats after burn injury. PRL and CS levels were determined in blood serum. STAT5 and phospho-STAT5 levels were determined in jejunum total protein extracts. The results confirmed an expected increase of CS between 4 and 6 h after the burn injury. Unexpectedly, PRL secretion was suppressed during the same time frame. These hormone levels returned to normal 6 to 8 h after burn injury. STAT5 was increased in the jejunum after burn injury, and its phosphorylation was increased between 8 and 11 h after burn injury. These changes in STAT5 were not temporally correlated with either the hormone changes that we observed or with previously documented changes of the gut function after burns.

Adrenocorticotropic Hormone↗
PubMed2000

The effect of burn injury on suppressors of cytokine signalling.

The newly identified suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway, and they act as a negative feedback loop by subsequently inhibiting the Jak/STAT pathway either by direct interaction with activated Jaks or with the receptors. In this study we investigated the expression and translation of SOCS proteins after burn injury. Thermal injury increased the expression of SOCS3 compared with sham at 4 h, 24 h, and 10 days after thermal injury in the liver. SOCS3 protein was increased at 4 and 24 h after thermal injury in the liver. Expression of SOCS1 mRNA was not detected in sham or burn liver. SOCS2 mRNA and cytokine-inducible SH2-containing protein (CIS) mRNA were detected at the same levels for both sham and burn at all time points in the liver. In the spleen there was a trend towards an increase in SOCS1 mRNA at all time points; thermal injury significantly decreased SOCS2 mRNA compared with sham at 4 h, SOCS3 mRNA was significantly increased at 24 h compared with 10 days, and CIS mRNA was detected at the same levels for both sham and burn at all time points. In conclusion, thermal injury causes elevations in SOCS3 within 4 h after a burn, reaching a maximum at 24 h post injury. Levels continue to be elevated for up to 10 days post injury. SOCS3 may be very important in regulating the balance between immunosuppression and inflammation after thermal injury.

Animals↗
PubMed1995

Ectopic substance P and calcitonin gene-related peptide immunoreactive fibres in the spinal cord of transgenic mice over-expressing nerve growth factor.

The aim of this study was to investigate the in vivo effects of CNS over-expression of nerve growth factor (NGF) on primary sensory neurons. To achieve this objective a transgenic mouse model was generated which bore a chick NGF gene driven by the myelin basic protein promoter. Northern blot analysis demonstrated that high levels of NGF mRNA were detected in the spinal cord of adult transgenic mice. Using immunocytochemistry NGF-immunoreactive (IR) oligodendrocytes were observed throughout the white matter. Furthermore, numerous ectopic substance P (SP)- and calcitonin gene-related peptide (CGRP)-IR fibres were detected in the white matter of the spinal cord of transgenic mice. NGF-IR oligodendrocytes and ectopic SP- and CGRP- fibres were entirely absent from control mice. In the cervical and lumbar dorsal root ganglia, the percentages of SP-IR neurons were significantly higher in transgenic mice when compared with controls. At the electron microscope level, ectopic SP- and CGRP-IR fibres were characterized as unmyelinated axons and axonal boutons. SP colocalized with CGRP in some of those axonal boutons and fibres. Capsaicin treatment of adult mice completely abolished the ectopic SP-IR fibres, confirming their primary sensory origin. Our results indicate that primary sensory neurons are responsive to NGF over-expression in the CNS. Ectopic SP- and CGRP-IR fibres in the white matter are likely to represent collateral sprouts of the central processes of the dorsal root ganglion cells which were triggered by NGF over-expressed in the myelinating oligodendrocytes in the spinal cord of transgenic mice.

Animals↗
PubMed1991

Plasticity of peptide biosynthesis in corticotropes: independent regulation of different steps in processing.

Compared to corticotropes in the adult rat anterior pituitary, neonatal corticotropes exhibit a significantly lower extent of conversion of precursor molecules into ACTH and a substantially greater extent of ACTH cleavage into smaller product peptides similar in size to alpha-melanotropin and corticotropin-like intermediate lobe peptide (CLIP). In the present study we examined pro-ACTH/endorphin (PAE; also called POMC) processing in corticotropes at different times during postnatal development to determine when these cells cease cleaving ACTH into smaller peptides and when they cease accumulating large amounts of intact precursor in vivo. The pattern of processing observed in the newborn is maintained through the second week after birth. A dramatic decrease in ACTH cleavage occurs between the second and third postnatal weeks. The extent of precursor cleavage increases toward the adult pattern by the fifth postnatal week. Explants of newborn anterior pituitary were previously shown to exhibit increased cleavage of ACTH into ACTH-(1-13)NH2 and CLIP, a process that was suppressed by glucocorticoids. To determine whether corticotropes from older animals maintained this plasticity and what intercellular interactions might be required, dissociated primary cultures were maintained in complete serum-free medium with or without added glucocorticoids. After 7 days in complete serum-free medium, the cellular content of both intact precursor and peptides the size of CLIP was increased compared to the corresponding in vivo pattern for animals from birth through adulthood. Although corticotropes from younger animals exhibited more pronounced changes when placed in culture, even cultures from adult animals exhibited some ACTH cleavage. For corticotrope cultures prepared from animals up to postnatal day 15, chronic treatment with dexamethasone did not suppress ACTH cleavage activity, although glucocorticoids did suppress ACTH cleavage in cultures from animals older than postnatal day 22. Biosynthetic labeling studies with cultures from 4- to 5-week-old rats demonstrated that the powerful suppressive effect of dexamethasone on the cleavage of newly synthesized ACTH-(1-39) was only evident 24 h after addition of the glucocorticoid to the culture medium. In contrast, removal of dexamethasone allowed cleavage of ACTH to commence within a few hours.

Adrenocorticotropic Hormone↗
PubMed1991

Investigation of the structural requirements for peptide precursor processing in AtT-20 cells using site-directed mutagenesis of proadrenocorticotropin/endorphin.

Mouse pro-ACTH/endorphin (or POMC) contains in its sequence each of the four possible pairs of basic amino acids recognized as potential cleavage sites in the production of bioactive peptides from higher mol wt precursors: KR (lysine-arginine), RR, RK, and KK. To examine the structural requirements for processing and routing in one region of pro-ACTH/endorphin, a reporter mutation was introduced into the mouse pro-ACTH/endorphin cDNA; a methionine residue was mutated to an isoleucine residue to allow biosynthetic double labeling with [3H]Ile and [35S]Met. Analysis of stable cell lines expressing the reporter cDNA indicated that this mutation did not affect processing or secretion. Therefore, additional mutations were introduced on the reporter background to investigate important structural features of the precursor. First, the tripeptide signal for N-linked glycosylation in the N-terminal glycopeptide (Asn65,Ser66,Ser67) was disrupted by the conservative substitution of asparagine65 with a glutamine residue. Secondly, O-glycosylation was prevented by substitution of threonine45 with an alanine residue. Finally, lysine50 was mutated to an arginine residue, transforming the RK doublet preceding the gamma 3MSH sequence into an RR doublet. The results show that the enzymatic machinery of AtT-20 cells fails to cleave efficiently at the Arg-Lys (RK) site even after elimination of any possible structural hindrance by carbohydrate side-chains. Elimination of O-linked oligosaccharides to the N-terminal side of gamma 3MSH did not allow cleavage at the RK site, and elimination of N-linked oligosaccharides did not alter the processing and routing of pro-ACTH/endorphin in AtT-20 cells. However, mutation of the RK sequence to RR allowed extensive cleavage regardless of the occurrence of O- or N-glycosylation.

Adrenocorticotropic Hormone↗
PubMed1991

The ordered secretion of bioactive peptides: oldest or newest first?

The order of secretion of newly synthesized and older bioactive peptides was investigated using primary rat intermediate pituitary melanotropes, which synthesize, store, and secrete peptides derived from pro-ACTH/endorphin (PAE; also POMC). PAE-derived peptides produced by the cells were biosynthetically labeled by incubating the cells with radioactive amino acids at various times preceding the period during which secretion was examined; secreted and cellular peptides were characterized and quantitated by immunoprecipitation, using affinity-purified antibodies to selected regions of PAE, followed by polyacrylamide gel electrophoretic analysis. Release in the absence of secretagogues (basal or constitutive release) was compared to release in the presence of maximally effective levels of 8-bromo-cAMP and BaCl2 (stimulated or regulated release). Both cell types showed short-lived preferential basal release of newly synthesized and not fully mature peptides (less than 2-3 h old). Conversely, the cells showed preferential stimulated secretion of older peptides. A process of maturation occurred, taking 2-4 h, after which the secretion of newly synthesized and older peptides in response to secretagogues was nearly indistinguishable for the smallest product peptides. The data support a model of gradual processing of peptides from precursors into smaller products and maturation from molecules only available for basal release into peptides available for stimulated secretion as well as for basal release. Basal secretion was found to include mature peptides as well as intermediates and precursor molecules. The data do not support the existence of any preferential regulated secretion of newly synthesized peptides.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Rapid effectiveness of prednisone and thionamides combined therapy in severe amiodarone iodine-induced thyrotoxicosis. Comparison of two groups of patients with apparently normal thyroid glands.

Treatment of amiodarone iodine-induced thyrotoxicosis is often unsuccessful. Nevertheless, severe forms require a rapidly efficient therapy. Twelve patients with severe amiodarone iodine-induced thyrotoxicosis, as demonstrated on clinical and biological findings, were studied. After amiodarone withdrawal, 6 patients (group A) were treated with thionamides alone (carbimazole 60 mg daily and benzylthiouracile 1.5 g daily), and 6 patients (group B) received in addition to the same antithyroid drugs prednisone, 0.50 to 1.25 mg/kg/day for 40 days; in group A, T4 levels did not change over the study period of 40 days; T3 levels decreased only after 30 days; clinical status did not improve. In group B: T3 and T4 levels decreased dramatically at 10 days of treatment, to values significantly lower than in group A; clinical improvement occurred mainly in patients treated with high doses of prednisone; elevated thyroglobulin levels diminished rapidly. Improvement was maintained after cessation of prednisone. The rapid effect of prednisone suggests an impairement of proteolysis of thyroglobulin possibly due to a lysosomal action.

Adult↗
PubMed1986

Breast cyst fluid proteins and breast cancer.

A specific breast cyst fluid protein was purified by the following steps: ultracentrifugation, gel filtration, DEAE and Con A chromatography, and gel filtration with guanidine, 6 M. The protein was pure, having a molecular weight of 17,800 daltons on SDS-PAGE and 68,000 daltons on gel filtration. The GCDFP 17,800 is immunologically distinct from other breast cyst fluid components and known milk and plasma proteins. A specific radioimmunoassay was developed and used to determine GCDFP 17,800 in 158 samples of breast cancer cytosol. The GCDFP 17,800 levels were significantly different between grade I tumors (mean of 813 ng protein per mg +/- 430 SEM) and grade III tumors (mean 184 ng protein per mg +/- 59 SEM) and were correlated with progesterone receptor values in postmenopausal women (Spearman's correlation, p = 0.03) but not in premenopausal women. The value of GCDFP 17,800 did not differ between the pre- and the postmenopausal women. By immunocytochemistry the intracellular localization of the GCDFP 17,800 was also found in relation to tumor grading and in correlation with PR values. GCDFP 17,800 appears as a hormone-induced protein of the breast cells. Its intracellular detection by means of radiolabeling allows a more sensitive and precise evaluation of the hormone-dependence of the breast cancer cells and emphasizes the heterogeneity of the tumor cell population.

Amino Acids↗
PubMed1985

Prognostic value of concentration of pregnancy-specific beta 1-glycoprotein (SP1) in serum of patients with breast cancer.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow-up. Values greater than 1 micrograms/1 were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level greater than 1 microgram/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 microgram/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than 1 microgram/1 died.

Breast Neoplasms↗