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Biomedical subjects

A Leroux

Publications and source records attributed to A Leroux.

At least 19 recordsLinked to original sources
PubMed2004

Upregulation of rat P23 (a member of the YjgF protein family) by fasting, glucose diet and fatty acid feeding.

In a previous study, we identified and purified a 99-amino-acid rat liver-kidney perchloric-acid-soluble 23-kDa protein (P23) which displays 30% identity with a highly conserved domain of heat shock proteins (HSPs), as well as an AT-rich 3' untranslated region, which has also been described to play a role in H70 mRNA life span and protein expression. An identical perchloric-acid-soluble protein inhibiting protein synthesis in a rabbit reticulocyte lysate system was also found 2 years later by another group. More recently, the novel, the YjgF, protein family has been described, comprising, 24 full-length homologues, including P23, highly conserved through evolution, and consisting of approximately 130 residues each and sharing a common ternary structure. Independent studies from different laboratories have provided various hypothetical functions for each of these proteins. The high degree of evolutionary conservation may suggest that these proteins play an important role in cellular regulation. Although the function of none of these proteins is known precisely, we present experimental evidence which, combined with the relationship to glucose-regulating protein revealed here, and the relationship to fatty-acid-binding protein revealed by others, allow us to propose a role for P23. In rat liver, P23 expression is developmentally regulated and modulated by dietary glucose, and its mRNA is induced by starvation, in the presence of fatty-acids and in 3-MeDAB-induced hepatomas. The mRNA encoding mouse liver P23 is also hormonally modulated in a mouse line AT1F8. These data indicate that P23 protein might be a key controller of intermediary metabolism during fasting.

Animals↗
PubMed2004

[Preoperative brachytherapy for clinical stage I and II endometrial carcinoma: results from a series of 780 patients with a 10-year follow-up].

AIMS OF THE STUDY: Retrospective analysis of patients treated by preoperative brachytherapy for endometrial carcinoma. PATIENTS AND METHODS: From 1973 to 1994, 780 consecutive patients with a clinical stage I-II endometrial carcinoma were treated with brachytherapy followed by surgery and pelvic irradiation if necessary. Tumour was staged according to 1979 UICC classification. There were 462 T1a, 257 T1b, and 61 T2, 62% were well differentiated. Brachytherapy consisted in one low dose rate endocavitary application. Sixty grays were delivered on the reference isodose. Surgery consisted in a TAH/BSO (Piver II) and was performed 6 weeks later. Nodal pelvic irradiation was indicated in case of unfavourable pathological prognostic factors. RESULTS: Median follow up was 122 months. Five year survival rates were: 84% for overall survival, 86% for survival without recurrence, 92.8% for local control, and 3.8% for late complications. Pronostic factors were age, stage, differentiation, grade and postoperative extension. Multivariate analysis showed only age, differentiation and postoperative extension to be independent prognostic factors. CONCLUSION: If for stage 1, initial surgery has now replaced preoperative brachytherapy in most cases because it allows to identify initial prognostic factors, preoperative brachytherapy remains the most interesting option for stage 2 endometrial carcinomas.

Adult↗
PubMed2004

Kinetics, biodistribution and therapeutic efficacy of hexylester 5-aminolevulinate induced photodynamic therapy in an orthotopic rat bladder tumor model.

PURPOSE: To optimize photodynamic therapy (PDT) we investigated the kinetics and biodistribution of hexylester 5-aminolevulinate (hALA) induced protoporphyrin IX (PpIX) and the therapeutic efficacy of PDT at different drug and light doses in an orthotopic rat bladder tumor model. MATERIALS AND METHODS: Healthy and tumor bearing rats were instilled intravesically with hALA (4, 8 and 16 mM) for 1 hour. Fluorescence was recorded spectroscopically in situ. PpIX fluorescence distribution and quantification across the bladders was visualized with fluorescence microscopy. PDT efficacy at different fluences (15 to 80 J/cm2) was histologically assessed 48 hours and 1 week after treatment. RESULTS: Spectroscopic analysis in normal or tumor bearing rats showed the highest tumor-to-normal ratios 2 or 3 hours after the end of the 8 or 16 mM hALA instillation (5.4 and 5.7, respectively). Within the same tumor bearing animal the same fluorescence levels were observed in normal epithelium and transitional cell carcinoma, whereas the tumor-to-muscle ratio was 3. Tumor necrosis with an intact normal bladder wall was observed with a fluence of 20 J/cm2 for 8 mM hALA, while 15 J/cm2 was ineffective and 25 J/cm2 induced total wall necrosis. Although it induced comparable PpIX fluorescence, 16 mM hALA did not result in tumor eradication at any fluence. CONCLUSIONS: An optimal PDT effect was obtained with 8 mM hALA and a fluence of 20 J/cm2. While different hALA concentrations ind uce identical PpIX fluorescence intensities, the PDT outcome was considerably different. Thus, fluorescence does not necessarily predict the therapeutic efficacy of PDT.

Aminolevulinic Acid↗
PubMed2004

Enhanced cell growth inhibition following PTEN nonviral gene transfer using polyethylenimine and photochemical internalization in endometrial cancer cells.

PTEN is a tumor suppressor gene mapped on chromosome 10q23.3 and encodes a dual specificity phosphatase. PTEN has major implication in PI3 kinase (PI3K) signal transduction pathway and negatively controls PI3 phosphorylation. It has been reported to be implicated in cell cycle progression and cell death control through inhibition of PI3K-Akt signal transduction pathway and in the control of cell migration and spreading through its interaction with focal adhesion kinase. Somatic mutations of PTEN are frequently detected in several cancer types including brain, prostate and endometrium with more than 30% of tumor tissue specimens bearing PTEN mutations and/or deletions. Because of its high frequency of mutations and its important function as tumor suppressor gene, PTEN is a good candidate for gene therapy. Inducible expression of PTEN has been also reported. In cancer cells bearing PTEN abnormalities, the reversion of PTEN function by external gene transfer becomes more and more investigated in cancer treatment research. Several technologies including the photochemical internalization (PCI) and aiming at improving the transfection efficiency have been reported. PCI is an innovative procedure based on light-induced delivery of macromolecules such as DNA, proteins and other therapeutic molecules from endocytic vesicles to the cytosol of target cells. PCI has been reported to enhance the gene delivery potential of viral and nonviral vectors. The present study was designed to evaluate the influence of photochemical internalization on polyethylenimine (PEI)-mediated PTEN gene transfer and its effects on the cellular viability in Ishikawa endometrial cancer cells bearing PTEN abnormalities. PCI was found to significantly (P < 0.01) enhance PTEN mRNA expression (4.2 fold increase). Subsequently, following PEI-mediated PTEN gene transfer, the restoration of the PTEN protein expression was observed. As a consequence, significant cell growth inhibition (44%) was observed in Ishikawa endometrial cells. Using PCI for PEI-mediated PTEN gene transfer was found to further enhance PTEN mRNA and protein expression as well as PTEN-related cell growth inhibition reaching 89%.

Cell Division↗
PubMed2002

A review of the adaptability and recovery of locomotion after spinal cord injury.

Spinal cord injury (SCI) is associated with multiple motor problems leading to the alteration and limited adaptation in the walking and postural behavior. This review addresses recent findings on locomotor and postural adaptations after spinal cord injury. The adaptation of the locomotor behavior to behavioral goals and external constraints constitute important functional prerequisites in the recovery of locomotion after spinal cord injury. Functional prerequisites in locomotion include coping with changes in speed, slope obstacle, weight support, interaction with walking aids, energy consumption and attentional demands. Various treatment approaches such as locomotor training using body weight support (BWS) and functional electrical stimulation (FES) will be discussed, in the context of functional prerequisites necessary in the recovery of locomotion. Understanding locomotor and postural adaptations will lead to a better appreciation of the normal and dysfunctional mechanisms, and culminate eventually in the development of appropriate rehabilitation assessment and treatment strategies.

Adaptation, Physiological↗
PubMed2001

Transcriptional and translational mechanisms of cytochrome b5 reductase isoenzyme generation in humans.

Cytochrome b5 reductase (b5R) is an essential enzyme that exists in soluble and membrane-bound isoforms, each with specific functions. In the rat, the two forms are generated from alternative transcripts differing in the first exons. In contrast, the biogenesis of b5R isoforms in the human is not yet well understood. In the present study we have detected three novel alternative exons, designated 1S, S' and 1B, located between the first alternative exon 1M and the common second exon in the human b5R gene. Accordingly, multiple M-type, S-type and SS'-type and B-type transcripts are generated. All types of human b5R transcript are expressed ubiquitously. An analysis of in vitro translation products demonstrated an alternative use of different AUG initiators resulting in the production of various human b5R protein isoforms. Our results indicate that the organization of the 5' region of the b5R gene is not conserved between rodents and humans. Insertion of Alu elements into the human b5R gene, in particular just upstream of the S/S' region, could be responsible for dynamic events of gene rearrangement during evolution.

Alternative Splicing↗
PubMed2000

[Results of large-scale clinical trials and medical practice].

The results of large scale clinical trials are part of the scientific data on which medical and, in particular therapeutic decisions, are base; very concordant data may even be used to define appropriate or inappropriate prescribing behaviour in the context of recommendations or references of good medical practice. Large scale clinical trials, however, have limitations inherent to their method; they give a mean result observed in an average population. The true question is to know if the therapeutic benefit proved in a therapeutic trial will be observed in a given individual in the future. If the aim of treatment is to make a symptom disappear or act on an objective intermediate criterion related to the prognosis, the benefits for the individual are easy to assess. When the aim is to prolong life or prevent a recurrence of a serious illness, the probability of avoiding a complication by treatment is only a statistic. This probability depends o: the amplitude of the therapeutic benefit observed in the trials; the resemblance of the patient to the "mean population" included in trials; the comparison of the treatment of the patient with the "mean treatment" used in the trials. An exact understanding of scientifically proven data then encounters the limits of the capacity of human memory. Probability medicine remains, however, the method which enables, for a given patient, the choice of treatment with the greatest chance of being effective, providing the elementary rules of utilisation of the information are respected.

Clinical Trials as Topic↗
PubMed1999

Adaptation of the walking pattern to uphill walking in normal and spinal-cord injured subjects.

Lower-limb movements and muscle-activity patterns were assessed from seven normal and seven ambulatory subjects with incomplete spinal-cord injury (SCI) during level and uphill treadmill walking (5, 10 and 15 degrees). Increasing the treadmill grade from 0 degrees to 15 degrees induced an increasingly flexed posture of the hip, knee and ankle during initial contact in all normal subjects, resulting in a larger excursion throughout stance. This adaptation process actually began in mid-swing with a graded increase in hip flexion and ankle dorsiflexion as well as a gradual decrease in knee extension. In SCI subjects, a similar trend was found at the hip joint for both swing and stance phases, whereas the knee angle showed very limited changes and the ankle angle showed large variations with grade throughout the walking cycle. A distinct coordination pattern between the hip and knee was observed in normal subjects, but not in SCI subjects during level walking. The same coordination pattern was preserved in all normal subjects and in five of seven SCI subjects during uphill walking. The duration of electromyographic (EMG) activity of thigh muscles was progressively increased during uphill walking, whereas no significant changes occurred in leg muscles. In SCI subjects, EMG durations of both thigh and leg muscles, which were already active throughout stance during level walking, were not significantly affected by uphill walking. The peak amplitude of EMG activity of the vastus lateralis, medial hamstrings, soleus, medial gastrocnemius and tibialis anterior was progressively increased during uphill walking in normal subjects. In SCI subjects, the peak amplitude of EMG activity of the medial hamstrings was adapted in a similar fashion, whereas the vastus lateralis, soleus and medial gastrocnemius showed very limited adaptation during uphill walking. We conclude that SCI subjects can adapt to uphill treadmill walking within certain limits, but they use different strategies to adapt to the changing locomotor demands.

Adaptation, Physiological↗
PubMed1999

Walking after spinal cord injury: evaluation, treatment, and functional recovery.

OBJECTIVE: To present some recent developments and concepts emerging from both animal and human studies aimed at enhancing recovery of walking after spinal cord injury (SCI). DATA SOURCES: Researchers in the field of restoration of walking after SCI, as well as references extracted from searches in the Medline computerized database. STUDY SELECTION: Studies that reported outcome measures of walking for spinal cord injured persons with an incomplete motor function loss or cats with either a complete or incomplete spinal section. DATA EXTRACTION: Data were extracted and validity was assessed by the authors. DATA SYNTHESIS: This review shows that a multitude of interventions--mechanical, electrical, or pharmacologic--can increase the walking abilities of persons with SCI who have incomplete motor function loss. CONCLUSIONS: A comprehensive evaluation of walking behavior requires tasks involving the different control variables. This comprehensive evaluation can be used to characterize the process of recovery of walking as well as the effectiveness of various treatments.

Animals↗
PubMed1999

Detection by immunohistochemistry of c-erbB2 oncoprotein in breast carcinomas and benign mammary lesions.

The presence of the c-erbB2 oncoprotein was demonstrated by immunohistochemistry in a study involving 173 mammary lesions. The lesions included infiltrating cancers, non-invasive neoplasia, as well as atypical and benign lesions. Our aim was to investigate the correlation between the c-erbB2 oncoprotein overexpression and the morphological features of the different mammary tissues analyzed to obtain a better characterization for the growth potential of certain lesions, with emphasis placed on the non-invasive neoplasia and the atypical lesions. Nearly 30% of infiltrating ductal carcinomas (27/89 cases) and 2 out of 24 infiltrating lobular carcinomas were positive. The comedocarcinomas were mostly stained (83%). In contrast, the intraductal carcinomas of cribriform or papillar patterns were consistently negative. No staining was observed in the atypical epithelial hyperplasia located in the vicinity of positive cancers for anti-oncoprotein c-erbB2 antibody. Furthermore, the only 5 positive cases for c-erbB2 out of 32 cancer-free cases were three fibroadenomas and two fibrocystic diseases with atypical ductal hyperplasia. A close correlation was thus observed between c-erbB2 oncoprotein overexpression and cancerous cell morphology, characterized by a marked nuclear hypertrophy often associated with cellular pleomorphism. However, predictive abnormalities of malignant transformation in non-neoplastic epithelial proliferation was difficult to identify, considering only the c-erbB2 expression. A group of tumors with little nuclear abnormalities were found positive for c-erbB2 immunostaining. These probably corresponded to a particular cellular phenotype. Further studies involving other oncogenes should lead to a better characterization of the different tumor phenotypes and help to clarify breast carcinogenesis.

Breast Neoplasms↗
PubMed1997

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Adolescent↗
PubMed1997

Investigation of quadriceps femoris function through electrical stimulation.

OBJECTIVE: Patellofemoral dysfunctions are associated with problems in the knee extensor mechanism, including specific atrophy of the distal fibers of the vastus medialis, also known as the vastus medialis oblique. Rehabilitation of the vastus medialis in patellofemoral dysfunctions has been shown to be ineffective. This limitation had stemmed from the lack of understanding of the vastus medialis' specific functions. The purpose of this project was to investigate the role of four portions of the quadriceps femoris using surface electrical stimulation. DESIGN AND SETTING: Single-group and single-test (repeated measures on muscle portions) design. All tests were performed in a university laboratory. SUBJECTS: Eight healthy university students received electrical stimulation. MEASUREMENTS: Subjects were seated with the knee at 90 degrees of flexion and the leg pushing against a strain gauge that measured the force exerted. Electrical stimulation was administered on the vastus lateralis, rectus femoris, and proximal and distal fibers of the vastus medialis to quantify the torque produced by the knee extensors. The electrical stimulation maximum intensity was adjusted to achieve specific fiber recruitment and the highest isolated contraction. Force was measured with a strain gauge placed on the anterior aspect of the distal end of the tibia. Force was recorded in two levels: force applied before the onset of electrical stimulation and force produced by the stimulation. Subjects also performed two maximum isometric knee extensions before and after electrical stimulation for normalization. RESULTS: Electrical stimulation elicited mean torques of 6.31 per thousand, 14.0 per thousand, 20.2 per thousand, and 28.0 per thousand of maximum isometric voluntary contractions of the distal and proximal fibers of the vastus medialis, the vastus lateralis, and rectus femoris, respectively. CONCLUSIONS: The distal fibers of the vastus medialis do not contribute significantly to knee extension.

Journal Article↗
PubMed1996

Prognostic factors for patients with localized primary malignant fibrous histiocytoma: a multicenter study of 216 patients with multivariate analysis.

BACKGROUND: The purpose of this study was to determine the independent prognostic variables in a well documented subset of 216 patients with localized primary malignant fibrous histiocytomas (MFH). METHODS: Between the years 1980 and 1989, 216 patients with localized, primary (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC] Stage I-IVA) MFH were evaluated and treated in 10 participating centers of the sarcoma group of the French Federation of Cancer Centers (FNCLCC). Clinicopathologic factors were collected retrospectively and entered into a cooperative database. Tissue slides of all cases were jointly reviewed microscopically by the pathology subcommittee. Surgical treatment was performed on all but 6 (3%) patients. One hundred ninety-five patients (90%) were free of gross disease, with complete local control at the end of the initial treatment. The adjuvant treatment was radiotherapy in 78 patients (36%), chemotherapy in 19 patients (9%), and both in 61 patients (28%). RESULTS: The median follow-up was 3.5 years (range, 45 days to 12 years). Five-year actuarial rates of disease specific (DSS), metastasis free (MFS), and local recurrence free (LRFS) survival were 70%, 63.3%, and 62.7%, respectively. Multivariate analyses showed that the adverse prognostic factors independently associated with decreased disease specific survival were UICC/AJC Stage III + IVA (P < 0.00001; relative risk [RR], 3.27; 95% confidence interval [CI], 1.6-6.58), residual macroscopic disease following primary local therapy (P = 0.00024; RR, 3.99, CI, 2.04-7.82), deep tumor location (P = 0.0045; RR, 3.37; CI, 1.21-9.38), non-myxoid histology (P = 0.0056; RR, 9.28; CI, 1.03-83.41), and age older than 50 years (P = 0.037; RR, 2.19; CI, 1.04-4.61). Two factors were significantly related to MFS in the patients with the poorest prognosis: histopathologic Grade 3 (P < 0.0001, RR, 3.46; CI, 2.02-5.91) and tumor size greater than 8 cm in largest dimension (P = 0.0012; RR, 2.78; CI, 1.36-3.66). With regard to LRFS, patients who did not undergo radiotherapy had reduced local control (P = 0.0043; RR, 2.36; CI, 1.46-3.83). CONCLUSIONS: Resection of all macroscopic disease was independently associated with improved disease specific survival and adjuvant radiotherapy significantly decreased the local relapse risk. Histopathologic grade was the most important prognostic factor for DSS and MFS.

Actuarial Analysis↗
PubMed1996

[Mesenteric vein infarction associated with congenital antithrombin III (ATIII) deficiency].

A venous mesenteric infarction in a 27-year-old patient is reported. This patient presented a genetic quantitative AT-III deficiency without anticoagulation therapy. Ultrasonography revealed portal vein thrombosis and laparoscopy showed mesenteric vein infarction. Laparotomy was performed mmediately and revealed segmental infarction of 60 cm of the jejunum which was resected; the portal vein was considered to be partially occluded on palpation. No strangulation or mechanical factors were identified. Immediately postoperatively the patient received therapeutic doses of heparin with AT-III concentrates to increase AT-III levels; no recurrent thrombotic episode was observed. A systematic second-look operation 24 hours postoperatively showed good bowel viability. Five days later, long-term anticoagulation with acenocoumarol was decided. Twelve days later, ultrasonography showed complete portal revascularization which was confirmed by a third surgical operation on D60.

Adult↗
PubMed1995

Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II.

Recessive congenital methemoglobinemia (RCM) due to NADH-cytochrome b5 reductase (cytb5r) deficiency leads to two different types of diseases. In the type I form, cyanosis is the only symptom, and the soluble enzyme is defective in red blood cells. In the type II form, cyanosis is associated with severe mental retardation and neurologic impairment; the enzymatic defect is systemic, involving both soluble and membrane-bound isoforms. We characterized mutations responsible for cytb5r deficiency in three unrelated patients with severe RCM type II. The first patient presented a homozygous exon 5 skipping. The only mutation detected was a homozygous G to C transversion at position +8, downstream from the 5' splice site of exon 5. We suggest that this unusual mutation might be responsible for the abnormal splicing of the primary transcripts, resulting in frameshift with premature STOP codon. The second mutation found corresponds to a homozygous C to T transition changing the Arg-218 codon to a premature STOP codon in exon 8. The third case was a compound heterozygote, carrying two different mutant alleles in the cyb5r gene. One allele presented a missense mutation with replacement of Cys-203 (TGC) by Arg (CGC) in exon 7. The second allele carried a 3-bp deletion (TGA) of nucleotides 815 to 817, modifying two contiguous codons in exon 9 of the cDNA with loss of Met-272. These results confirm the genetic polymorphism of cytb5r gene mutations identified in RCM type II, as observed for the mutations described in the RCM type I, and shed light on the molecular bases of the two different diseases associated with cytb5r deficiency.

Amino Acid Sequence↗
PubMed1995

Pain effect on monosynaptic and polysynaptic reflex inhibition.

OBJECTIVE: Determine the electrophysiological effects of anterior knee pain using monosynaptic and polysynaptic reflexes. DESIGN: A pretest/posttest control group experimental design with repeated measures. SETTING: All tests were performed in a university laboratory. PARTICIPANTS: Six subjects suffering from patello-femoral dysfunction (PFD) composed the experimental group. These patients were diagnosed and referred by medical and chiropractic doctors. Six healthy subjects were recruited for the control group. INTERVENTION: Pain relief by cold application (10 minutes) on the knee. MAIN OUTCOME MEASURES: Monosynaptic reflex: H reflex of the superficial portions of the quadriceps femoris. Polysynaptic reflexes: nociceptive flexion response (NFR) of the long head of the biceps femoris. RESULTS: Cold application, producing significant pain relief (p < 0.05), did not change H-reflex amplitude (p > 0.05) for both groups and did not show modulation of the NFR. However, the PFD group showed significantly lower pain (p < 0.05) and NFR thresholds (p < 0.05) than the control group. Finally, nociceptive stimulation was applied at the sural nerve during an isometric extension of the knee (20% of maximum electromyographic contraction). After this stimulation, uni-articular extensors, especially the distal fibers of the vastus medialis, showed a longer and stronger inhibition than the bi-articular rectus femoris. CONCLUSIONS: Pain episodes do not appear to affect monosynaptic responses. NFR threshold differences found between PFD and control group could be explained by the increased excitability of the nervous system in subjects experimenting painful bouts. Functional implications of these findings are discussed.

Adult↗