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Biomedical subjects

S Jacques

Publications and source records attributed to S Jacques.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Photodynamic therapy with chloroaluminum-sulfonated phthalocyanine.

To study the vascular effects of a new photosensitizing agent independent of the influence of tumor growth, a cutaneous wound model was used. Six-week-old Harlan-Sprague-Dawley "Fuzzy" rats were surgically wounded in a standard fashion. The animals were then divided into three groups: the first group received chloroaluminum-sulfonated phthalocyanine only, the second group was treated with light only, and a third group was treated with both chloroaluminum-sulfonated phthalocyanine and light. Photodynamic therapy with chloroaluminum-sulfonated phthalocyanine had a direct effect on the neovasculature of a healing wound. The vasodilatation that was seen in the wound neovasculature that occurred 12 hours after the completion of chloroaluminum-sulfonated phthalocyanine-photodynamic therapy may have indicated a therapeutic "window" at which other therapies can be employed to improve clinical efficacy.

Animals

Photodynamic therapy with chloroaluminum sulfonated phthalocyanine in the rat window chamber.

The efficacy of photodynamic therapy tumor destruction is dependent upon both the interruption of the tumor vasculature and the resultant production of unstable oxygen species causing cellular oxidation and death. Chloroaluminum sulfonated phthalocyanine (CASP) is a recently developed photosensitizer. In order to study the direct vascular effects of CASP on a non-tumor system, a rat window chamber was utilized. Twelve rats were implanted with the window chamber, and were divided into two groups of six. Three rats served as controls for each group (receiving light alone, CASP alone, or no treatment). The remaining 6 rats received 10 mg/kg CASP intravenously 4 days after chamber placement. Photoactivation with light was performed 24 hours after injection (power density 200 mW/cm2, irradiance 100 J/cm2, lambda = 675 nm). Utilizing integrating sphere measurements and image analysis, marked vascular changes in the form of initial vasospasm followed by vaso-constriction and loss of chamber neovascularization were noted in the CASP-PDT group. The control groups exhibited no significant changes. Manipulation of the chamber vasculature at strategic time-points may translate into improved response rates for photodynamic therapy in a tumor model.

Animals

Salvage immunotherapy of malignant glioma.

We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

Adult

Preliminary clinical trial of immunotherapy for malignant glioma.

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Adult

Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function.

The radiopharmaceutical, metaiodobenzylguanidine (MIBG) acts as an analog of norepinephrine (NE). Experiments in rats were carried out to determine how closely the movements of [125I]MIBG in the heart mimicked those of [3H]NE, and if the changes [125I] MIBG concentrations would reflect injury to, and function of, adrenergic neurons in the heart. Injury to adrenergic neurons by 6-hydroxydopamine substantially reduced the uptake of [125I] MIBG into the left ventricle, but the effect was less than that on uptake of [3H]NE uptake and concentration of endogenous NE. Similarly, when desmethylimipramine was given to inhibit the uptake-1 pathway of neurons, the reduction in uptake of [125I]MIBG was statistically significant but less than that of [3H]NE; part of this difference may be attributable to partial uptake of [125I]MIBG into neurons by a diffusion pathway. Substantial fractions of [125I]MIBG and [3H]NE were displaced from the heart by the sympathomimetic drug, phenylpropanolamine. When adrenergic neurons of the heart were stimulated by feeding of rats, the disappearance rates of [3H]NE and [125I]MIBG from the heart were significantly increased. Although not a perfect analog of [3H]NE, [125I]MIBG appears to enter and leave the heart in patterns similar to those of [3H]NE. Thus, movements of [125I]MIBG give indices of adrenergic neuron injury and function in the heart.

3-Iodobenzylguanidine

A route to home.

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Humans

Benign intracranial hypertension in pregnancy.

Benign intracranial hypertension, an unusual case of headaches, was associated with pregnancy in a gravid female with the chief complaint of headache. Symptoms resolved after three days of prednisone therapy. In benign intracranial hypertension, the possibilities of intracranial mass lesions, intracranial infection, obstruction of the cerebral ventricles, and hypertensive encephalopathy are excluded by evaluation with skull films, computerized axial tomography, electroencephalography and lumbar puncture. The only symptom may be headache and the only physical sign, papilledema. Therefore, neurological examination must include visualization of the fundi.

Adult

Brain stimulation and reward: "pleasure centers" after twenty-five years.

"Self-stimulation" is a phenomenon whereby an animal (including a human being) will repeatedly stimulate its brain electrically, sometimes to the point of exhaustion. This phenomenon is robust and readily reproducible in many areas of the brain, particularly in nuclei and fiber tracts known to be monoaminergic, and it has been the basis for the study of reinforcement and learning mechanisms in the brain. The last 25 years of work on intracranial self-stimulation is reviewed with an emphasis on mechanisms, primarily catecholaminergic. Implications for learning and pain mechanisms are discussed.

Acetylcholine

Evaluation of electrode array material for neural prostheses.

Matrix support materials for brain surface electrodes used in neuroprosthetic applications were evaluated after chronic subdural implantation over the parietal cortex of the cat. Four types of array fabricated with Silastic, Dacron mesh, or platinum wire annuli were implanted for periods ranging from 5 weeks to 1 year. We evaluated the arrays by access resistance measurements and gross and histological observations of the tissue beneath both nonstimulated and stimulated electrodes. A porous type matrix constructed of Dacron mesh proved to be the superior design because of its minimal compression of the cortical surface, facility of handling during implantation and autopsy, and satisfactory electrical characteristics provided by a good electrode-brain interface. (Neurosurgery, 5: 681--686, 1979).

Animals

Microsurgical cannulation of the thoracic duct in cats. Technical note.

The authors describe a new technique for the microsurgical cannulation of the thoracic duct. A small silastic tube is utilized which can be joined to a subcutaneously implanted one-way flow, CSF, Ommaya-type reservoir. Extended drainage is avoided. No deletion or alteration of major venous channels occurs. Lymph collection is accomplished by tapping the subcutaneous reservoir with a small-bore needle.

Animals

Improved cognition after external carotid endarterectomy.

Recent clinical results support the conclusion that internal carotid endarterectomy not only serves as a prophylactic measure against catastrophic stroke, but may improve cognitive functioning as well. Improvement in cognitive testing after internal carotid endarterectomy has been amply substantiated in recent literature. 3, 4, 5, 8, This report illustrates that improvement in cerebral blood flow by any means is equally effective in improving cerebral function.

Aged