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Biomedical subjects

S Jacques

Publications and source records attributed to S Jacques.

At least 37 records · Page 2Linked to original sources

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↗

Cognitive information processing and learning mechanisms of the brain.

The view that the two cerebral hemispheres of the human brain are characterized by different cognitive processing modes that handle information received in various forms is commonly accepted by neurobehavioral scientists and neuropsychologists. Selected neuroanatomical, electrophysiological, neurochemical, biochemical, and neuropsychological data that bear on a cognitive information-processing model of the brain are presented. Processes involved in memory functions are discussed in regard to the nature of thought and the characteristics of mental life, e.g., internalization of thought, perception, arousal, attention, cognitive development, problem solving, the development of cognitive encoding, and selective recall. We present a position that argues for the brain as being flexible vs. fixed in its characteristics and limitations, drawing from various theories and viewpoints. We also present a review of selected mechanisms believed to be involved in brain-behavior processes, e.g., learning, cognition, pain, emotion, reward, cognitive development, and memory formation. A major theme addressed in terms of human information processing is that cognitive functioning, in a variety of instances, comprises subsets of more general processes, e.g., selective recall, cueing that is capable of addressing schemas, notions of inhibition and disinhibition, and the modulation of excitatory properties of certain neural transmitter substances. Questions such as "how is information stored in memory in the first place?" and "how do elements of motivation (i.e., goal orientation) get connected and then send their messages to appropriate inbound behaviors?" are addressed from the point of view that learning, although not understood completely, is somehow involved. Another unresolved question of theoretical and practical significance that we address is "how does learning result in neural connections?" Such questions are discussed in light of their implications for human memory, thought, and behavioral events.

Arousal↗

Development of a protocol for photoradiation therapy of malignant brain tumors: part 1. Photosensitization of normal brain tissue with hematoporphyrin derivative.

The successful application of phototherapy to subcutaneous tumors has suggested that a similar procedure should be developed for treating gliomas. As a result, attempts are being made to determine a set of conditions that would optimize the destruction of tumor cells while minimizing injury to surrounding brain tissue. To initiate this task, we developed a novel assay method to assess the amount of phototoxicity induced in normal brain by light exposure of mice treated with hematoporphyrin derivative (HPD). The application of this procedure demonstrated that a sufficient amount of HPD was retained in brain tissue, even 72 hours after injection, to cause severe cerebral damage in light-treated mice.

Animals↗

Cerebral gliomas.

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Brain Neoplasms↗

Regulation of pyrimidine and arginine biosynthesis investigated by the use of phaseolotoxin and 5-Fluorouracil.

Purified phaseolotoxin inhibits the growth of carrot cells. Such inhibitions can be reversed completely by citrulline but not by arginine. This toxin inhibits ornithine transcarbamylase activity in vitro, which leads to an accumulation of ornithine and a decrease in arginine levels intracellularly. In carrot cells, 5-fluorouracil (5-FU) toxicity can be reduced by the addition of purified toxin and citrulline, or ornithine. The toxin also decreases the incorporation of [(14)C]uracil and [(14)C]5-FU into trichloroacetic acid precipitable material by 50%. Finally, a 5-FU-resistant line, F5 (Sung ZR, Jacques S 1980 Planta 148: 389-396), was found to be more sensitive to the toxin than were 5-FU-sensitive cells. One millimolar 5-FU roughly doubled the ability of F5 to tolerate phaseolotoxin. These results demonstrate a close regulation between the pyrimidine and arginine path-ways in carrots.

Journal Article↗

Dopaminergic (DA) systems: their role in pathological neurobehavioral symptoms.

Two established dopamine (DA) systems (i.e., the nigrostriatal and the mesolimbic-mesocortical) are the focus of this article. Their neuroanatomy is briefly outlined to relate neurochemical with neurobehavioral events and alterations in DA-affected systems with the behavioral consequence. Selected theories and major ideas related to DA systems and their implicated role in neurobehavioral symptoms that have emerged over the last decade are included. Correlations with behavioral consequences of disturbances in DA systems lack clarity as to precisely known clinical effects relating to human behavioral and motor acts. The purpose of this article is to review selectively the literature pertaining to two of the six major DA mechanisms. The principal question addressed in this article is, "How do DA mechanisms promote neurobehavioral consequences such as the symptoms of schizophrenia?" Other topics covered include Parkinson's disease, Huntington's chorea, and intracranial self-stimulation drive-reward mechanisms. These clinical features and their possible underlying basis are discussed in terms of evidence suggesting that DA neurotransmitter alterations are likely to be several steps removed from a primary causal locus, which has more than one biochemical or neurotransmitter mechanism.

Animals↗

Histological evaluation of neural damage from electrical stimulation: considerations for the selection of parameters for clinical application.

The relationship of charge density per phase, or QD/ph (expressed in units of microcoulombs per cm2 per phase of the charge-balanced wave form), and total charge (QDt) to neural damage has been investigated by light and electron microscopy after surface stimulation of the parietal cortex in normal cats. QD/ph values ranging from 40 to 400 were achieved by varying several stimulus parameters. The least amount of neural damage in this study was observed at QD/ph 40). The extent of neural injury at stimulated sites increased with the charge density and was evident as disruption of cell membranes, intracytoplasmic vacoulation, an increasing glycogen content, the deposition of intracellular calcium hydroxyapatite, and neuronal and astrocytic degeneration. Although individual factors contributing to neural damage are isolated with difficulty, charge density and total charge seem to be predominant among the contributing parameters. In view of these findings, recommendations have been made for the selection of electrical stimulus parameters to be used in central nervous system prostheses.

Animals↗

A computerized microstereotactic method to approach, 3-dimensionally reconstruct, remove and adjuvantly treat small CNS lesions.

The authors update a novel method recently utilized in humans with various CNS pathology for stereotactic localization, removal, and adjuvant therapy of small CNS lesions using additional computer processing of the date from a GE 8800 CT Scanner. Multiple computer algorithms developed at Cal Tech enhance regions of interest by filtering, magnifying, color-coding and 3-dimensional reconstruction based on routine CT scans. This stereotactic approach is calculated by the computer and coordinates are mated to a modified head fixation system; small lesions can be removed with the apparatus described herein under direct binocular vision with minimal tissue damage. This technique may offer the possibility of successful secondary application of adjuvant therapy to, particularly, a CNS glioma site.

Brain↗