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Biomedical subjects

S Jacques

Publications and source records attributed to S Jacques.

At least 19 recordsLinked to original sources
PubMed2001

The Flexible Item Selection Task (FIST): a measure of executive function in preschoolers.

Abstraction and cognitive flexibility were assessed in 197 preschool children at 2, 3, 4, and 5 years of age using the Flexible Item Selection Task, a task adapted from the Visual-Verbal Test (Feldman & Drasgow, 1951). On this new inductive task, children were shown a set of 3 cards and required to select 2 cards that matched each other on 1 dimension (Selection 1) and then to select a different pair of cards that matched each other on another dimension (Selection 2). Thus, 1 of the 3 cards always had to be selected twice according to different dimensions. Two-year-olds failed to understand basic task requirements as assessed by a criterial measure. Three-year-olds did more poorly on Selection 1 than 4- and 5-year-olds (who performed near ceiling), suggesting that 3-year-olds had difficulty with the abstraction component of the task. Four-year-olds did worse than 5-year-olds on Selection 2, suggesting that they had difficulty with the cognitive flexibility component (i.e., difficulty selecting the same card on more than 1 dimension). Results are discussed in terms of the development of executive function.

Age Factors↗
PubMed2001

Poliovirus persistence in human cells in vitro.

Poliovirus (PV) can persist in vivo in the intestine of immunocompromised hosts for years. Moreover, immunocompetent individuals who have survived paralytic poliomyelitis sometimes develop the post-poliomyelitis syndrome (PPS), consisting of a variety of symptoms including new muscular atrophies. PPS may be due to PV persistence. We have developed models of PV persistence in neural cells and epidermoid cells. Cell determinants are of crucial importance for the establishment of persistent infections in human neuronal cells, whereas viral determinants play the primary role in human epidermoid HEp-2 cells. The results obtained with these in vitro models show the capacity of PV to persist and reveal a virus and cell co-evolution involving PV-receptor interactions. In addition, they suggest that several mechanisms are used by PV to establish and maintain persistent infections.

Animals↗
PubMed2000

Time- and space-resolved dynamic studies on ceramic and cementitious materials.

A review is given of the results and lessons arising from a sustained in situ diffraction study of the structure and performance of functional ceramic/cementitious materials in which synchrotron-based energy-dispersive diffraction has been the central under-pinning technique. Five particular points of discussion emerge: the demands on time resolution; the use of penetrating radiation for the in situ mode; the need for complementary techniques; re-analysing of data; spatially resolved diffraction: a new tomography. These aspects are discussed in turn using illustrative examples taken from the fields of cement hydration, clay intercalation, cation-exchanged zeolites, and particulate/fluid invasion into building and archaeological objects.

Journal Article↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed1999

Activation of neurotransplants in humans.

Clinical studies report symptomatic benefit in most fetal neurotransplantation treated Parkinson's disease patients. The underlying mechanism is incompletely explained. We investigated whether neural connections between host and transplanted tissue are established. Two Parkinson's disease patients with clinically excellent outcome after transplantation were studied with functional magnetic resonance imaging. A repetitive motor task that provided robust stimulation in the contralateral putamen in volunteers activated graft bearing regions of putamen in patients. In response to contralateral motor tasks, activation was recorded consistently in left putamen in patient 1 and in right putamen in patient 2. Functional magnetic resonance imaging suggests that neuronal rewiring contributes to the functioning of neurotransplants in vivo in humans.

Adult↗
PubMed1999

Rule selection versus rule execution in preschoolers: an error-detection approach.

In 2 experiments, an error-detection approach was used to determine whether 3-year-olds' perseverative errors on the postswitch phase of the Dimensional Change Card Sort (DCCS) are due to lack of response control or representational inflexibility. In Experiment 1, 3-, 4-, and 5-year-olds watched a puppet sort perseveratively on the postswitch phase and evaluated its responses. Most 4- and 5-year-olds detected the puppet's perseverative errors, whereas most 3-year-olds failed to do so despite detecting errors on a simpler card sort. Experiment 2 revealed that 3-year-olds who failed to correctly evaluate the puppet's behavior tended to fail their own DCCS. Results imply that perseveration on the DCCS cannot be attributed to difficulty inhibiting prepotent motor responses. Instead, changes in rule use between 3 and 5 years of age are interpreted in terms of the development of representational flexibility.

Age Factors↗
PubMed1998

Safety of intrastriatal neurotransplantation for Huntington's disease patients.

Fetal neural transplantation has been shown to be a feasible, safe, and according to a number of recent reports, effective treatment for Parkinson's disease (PD). Fetal striatal transplantation may be as feasible, safe, and effective a treatment for Huntington's disease (HD), a disorder for which there is currently no effective treatment. This report describes our experience with fetal striatal transplantation to adult striatum in three HD patients. Three moderately advanced, nondemented HD patients received transplantation of fetal striatal tissue. The striatal precursor was selectively obtained from the lateral ganglionic eminence. Each patient received bilateral grafts from five to eight donors, placed into the caudate nucleus (one graft on each side) and the putamen (four grafts on each side). All three patients had HD as documented by family history, DNA heterozygosity (17-20 and 48-51 repeats), magnetic resonance imaging (MRI) revealing striatal atrophy, and 2-deoxyglucose positron emission tomography revealing striatal hypometabolism. All patients had been evaluated using the Unified Huntington's Disease Rating Scale and appropriate neuropsychological tests for at least 3 months prior to transplantation. One year following transplantation, MRI of all three patients revealed that the grafts survived and grew within the striatum without displacing the surrounding tissue. No patients demonstrated adverse effects of the surgery or the associated cyclosporin immunosuppression, nor did any patient exhibit deterioration following the procedure. The limited experience provided by these three patients indicates that fetal tissue transplantation can be performed in HD patients without unexpected complications.

Adult↗
PubMed1994

Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.

BACKGROUND: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a sequence-specific manner, and thereby couple tyrosine phosphorylation to changes in the localization or catalytic activity of signal transducing molecules. Current understanding of SH2 specificity is based on the structures of SH2-peptide complexes of the closely-related Src and Lck tyrosine kinases. The tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent from those of the tyrosine kinases, with distinct target specificities, and is thus well suited for structural studies aimed at extending our understanding of SH2 specificity. RESULTS: Crystal structures of the amino-terminal SH2 domain of Syp in separate complexes with two high-affinity peptides, in complex with a non-specific peptide and in the uncomplexed form have been determined at between 2 A and 3 A resolution. The structure of the SH2 domain and the mode of high-affinity peptide binding is essentially similar to that seen in the Src and Lck structures. However, the binding interface is more extensive in Syp. CONCLUSIONS: Most SH2 targets have hydrophobic residues at the third position following the phosphotyrosine, and the Syp structure confirms that the peptide is anchored to the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp structure has revealed that sequence specificity can extend across the five residues following the phosphotyrosine, and has shown how the SH2 domain's surface topography can be altered with resulting changes in specificity, while conserving the structure of the central core of the domain.

Amino Acid Sequence↗
PubMed1994

Cerebral metabolic changes induced by MK-801: a 1D (phosphorus and proton) and 2D (proton) in vivo NMR spectroscopy study.

The dynamic effects of the non-competitive NMDA receptor antagonist, MK-801 on brain metabolism were investigated over 105 minutes in unanesthetized rats by proton and phosphorus NMR spectroscopy. MK-801 (0.5 and 5 mg/kg, i.p) induced no changes in intracellular pH, and in phosphocreatine, ATP, and inorganic phosphate levels, indicating that the drug preserved energy and intracellular pH homeostasis. There were transient increases in lactate after both doses of MK-801, suggesting early activation of glycolysis, which was not immediately matched by enhanced oxidative metabolism or by enhanced blood flow. Thereafter, lactate control level was not restored after 0.5 mg/kg whereas it was restored after 5 mg/kg in spite of a sustained metabolic activation. The low dose of MK-801 also caused a continuous decrease in cerebral aspartate level (-38%) which is thought to match the enhanced energy demand, whereas the high dose caused shorter and smaller changes. The intracerebral glucose level rose after MK-801 injection, indicating that brain tissue had an adequate or even excessive supply of glucose. Glucose time course seemed to closely match the changes in blood flow elicited by MK-801. This is the first study giving the metabolic pattern of a pharmacological activation. We demonstrate an excess of glycolysis over oxidative metabolism in the early time similar to that following physiological and pathophysiological states such as photic stimulation and seizures. The difference between the effects of the two doses of MK-801 suggests that the adjustment of cerebral metabolism to MK-801 activation is faster and greater with the high dose than with the low dose.

Animals↗
PubMed1993

Tumor specific response to photodynamic therapy.

The exact mechanism by which photodynamic therapy (PDT) causes tumor destruction has not been elucidated. Early reports indicated that PDT causes direct cellular effects probably mediated by unstable oxygen species, resulting in cellular oxidation and death. More recently, PDT effects on tumor blood flow have been implicated, and there are questions as to whether the PDT response is specific to tumor tissue. Rats were implanted with a window chamber containing either a mammary adenocarcinoma or a piece of inert surgical sponge. After growth of the tumor was ascertained, all rats were given 5 mg/kg Photofrin intraperitoneally, and then were irradiated with 630 nm light 24 hours post-injection. Caliper thickness and reflectance measurements were performed before and after irradiation; all animals were sacrificed 72 hours post-PDT and the chambers submitted for histologic analysis. Animals implanted with tumors demonstrated marked edema of the chamber with an associated decrease in reflectance. No edema response was noted in the chambers containing inert sponge, or in any controls. Nonselective PDT effects (characterized by a marked foreign body response) in chambers containing sponge was not seen. Histologic analysis of treated specimens corroborate the above data.

Animals↗
PubMed1993

Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA.

Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumor in vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safe in vivo and more effective than IL-2 triggering enhanced effector function in vitro.

Adrenal Cortex Hormones↗
PubMed1992

Twenty-two years screening for toxoplasmosis in pregnancy: Liege-Belgium.

Between 1966 and 1987, in Liége--Belgium, 20,901 pregnant women were screened for toxoplasmosis. In this period an increase in seronegative women from 30% to 53% and a decrease in the seroconversion rate from 6.4% to 1.2% was observed. This decrease could be the result of advice and prophylactic measures. Due to the low rate of seroconversion (actually less than 1%), the cost/effectiveness of a systematic screening and fetal diagnosis should be investigated.

Belgium↗
PubMed1991

Low-resolution structure of recombinant human granulocyte-macrophage colony stimulating factor.

A recombinant form of human granulocyte-macrophage colony stimulating factor (GM-CSF) which contains no carbohydrate has been crystallized. Multiple isomorphous replacement analysis using five heavy-atom derivatives has yielded an image of the structure at 6 A resolution that showed two molecules per asymmetric unit and allowed determination of the non-crystallographic symmetry transformation. The 6 A resolution result shows that the core of GM-CSF consists of four helices. The angles at which the helices pack together distinguishes this structure from known antiparallel four-helix bundle proteins. Consideration of the amino acid sequence properties and previous structural characterizations of GM-CSF leads to an assignment of the probable protein segments that form the helices.

Granulocyte-Macrophage Colony-Stimulating Factor↗
PubMed1991

Generation of stimulated, lymphokine activated T killer (T-LAK) cells from the peripheral blood of normal donors and adult patients with recurrent glioblastoma.

Peripheral blood mononuclear cells (PBM) from normal donors and patients with recurrent glioma were activated initially for 48-72 h with phytohemagglutinin-P (PHA) and recombinant human interleukin-2 (IL-2), and then proliferated in vitro for up to 5 months with IL-2. These cells are termed mitogen-stimulated lymphokine-activated T killer (T-LAK) cells. We measured patterns of T-LAK cell growth, in vitro cytolytic activity on a panel of continuous and primary tumor cells, and the phenotypes of the cells in these cultures. Lymphocyte viability declined dramatically over the first 3-5 days; and then the remaining cells in these cultures began to divide and maintained a constant 30-36 h doubling time for long periods in vitro. Phenotyping revealed that cells in the initial few days of culture were heterogeneous, but became almost totally CD3 T cells after 7-10 days in culture. The T-LAK cells from individual normal donors and cancer patients demonstrated a non-genetically restricted cytolytic ability against a panel of both continuous cell lines and primary autologous and allogeneic glioblastoma cells in vitro. This technique provides a method of generating large numbers of autologous cytolytic T cells with non-restricted anti-tumor activity that can be derived from peripheral blood mononuclear cells.

Adult↗
PubMed1991

An implantable tumor-window chamber model for the study of photodynamic therapy.

In order to study both the anti-tumor effects and early vascular events in photodynamic therapy, a useful animal model has been developed. A window chamber is surgically placed on the dorsum of the Fischer-344 rat, and 500-microns fragments of the rat mammary adenocarcinoma 13672 are placed under direct vision into the subcutaneous tissue. Implantation of the chamber has been successfully completed in more than 50 rats. The operative procedure is straightforward and is accomplished in less than 1 hour. Using tumor fragments, tumor viability has been 60%. We have demonstrated obvious and reproducible neovascularization occurring as soon as 1 day after implantation. The application of this system to an experimental protocol comparing the photosensitizers dihematoporphyrin ether (DHE) and chloraluminum sulfonated phthalocyanine (CASP) has yielded important information on early vascular events resulting from photodynamic therapy.

Adenocarcinoma↗
PubMed1991

Chloroaluminum sulfonated phthalocyanine versus dihematoporphyrin ether: early vascular events in the rat window chamber.

The development of a simple and well-tolerated rat window chamber has allowed direct comparison of the vascular effects of two photosensitizers, chloroaluminum sulfonated phthalocyanine (CASP) and dihematoporphyrin ether (DHE). CASP and DHE were given 4 days after the implantation of the window chamber. Photodynamic therapy (PDT) with CASP was performed 24 hours after intravenous injection (10 mg/kg) with light at 675 nm (power density 200 mW/cm2, incident energy 100 J). DHE was given in a similar fashion (5 mg/kg intraperitoneally; light at 630 nm with matching power density and energy settings 24 hours after injection). Using videomicroscopic and integrating sphere measurements, marked differences were noted in the vascular effects of these photosensitizers. DHE caused immediate hemorrhage and disruption of the postcapillary venules, while CASP induced vascular spasm starting 4 hours after the completion of PDT. Forty-eight hours after PDT, both systems demonstrated a loss of chamber-induced neovascularization.

Animals↗
PubMed1991

Therapy of recurrent high-grade gliomas with surgery, autologous mitogen-activated IL-2-stimulated (MAK) killer lymphocytes, and rIL-2: II. Correlation of survival with MAK cell tumor necrosis factor production in vitro.

Seven patients with recurrent high-grade glioma were treated in a Phase I/II trial with surgical debulking, after which mitogen-activated IL-2-stimulated killer (MAK) lymphocytes and 10(5) units rIL-2 were implanted in the surgical defect. The therapy was well tolerated, and the mean survival of this group of patients was 29 weeks. Tumor necrosis factor (TNF) production by MAK lymphocytes stimulated with IL-2 in vitro was measured. A significant (r = .78, p = .04) correlation between survival of patients after therapy and the ability of the MAK lymphocytes to produce TNF in vitro was noted. A significant negative correlation (r = -.82, p = .02) was found when comparing TNF production and increasing tumor size measured on MRI. No correlation was found between TNF production in vitro and MAK lymphocytes lytic activity on K562 and U373 target cells. No correlation was found between survival and MAK cell lytic activity measured on K562 and U373 target cells. We conclude that TNF production in vitro and cytotoxic activity measured in vitro are measures of different antitumor activity in vivo and in vitro. TNF production during IL-2-stimulated proliferation may be an important in vitro assay in terms of predicting length of survival of recurrent high-grade gliomas.

Adult↗