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Biomedical subjects

K G Go

Publications and source records attributed to K G Go.

At least 55 records · Page 3Linked to original sources

Cystic lesions of the brain. A classification based on pathogenesis, with consideration of histological and radiological features.

A classification of the existing multitude of cystic lesions of the brain is proposed, which allows an understanding of their genesis and consequent therapeutic implications, as well as their diagnostic characteristics. Essentially, cerebral cystic lesions may be classified into the following categories: Cysts containing CSF-like fluid, which include ex vacuo type cysts, such as leptomeningeal cysts, and cysts following surgical resection; cysts with fluid secreting walls and CSF-like content, such as arachnoid cysts; cysts associated with dysgenesis, for example Dandy-Walker cysts. The ex vacuo cysts increase craniospinal compliance, whereas the other cysts with CSF-like content do not; they are not per se expansive, however, although their occasional location along CSF pathways may cause obstruction and hydrocephalus. Another category includes cysts with a lining of non-neural epithelium like colloid cysts, epidermoid cysts, or craniopharyngiomas. They may increase in size and cause symptoms by compression, although not at the rate of tumour-associated cysts. The cysts associated with gliomas and other tumours have a pathogenesis bearing upon blood-brain barrier impairment and formation of vasogenic oedema. Finally, one may distinguish a category of cysts with infectious origin, such as brain abscesses and hydatid cysts. The cysts with CSF-like contents may be recognised by their magnetic resonance characteristics resembling those of CSF, whereas cysts containing proteinaceous fluid are associated with blood-brain barrier impairment and consequent contrast enhancement. The cysts with a lining of non-neural epithelium exhibit diverse properties of attenuation on computed tomography (CT) and magnetic resonance imaging (MRI), depending on the nature of their cyst contents.

Brain↗

Our approach towards developing a specific tumour-targeted MRI contrast agent for the brain.

This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.

Animals↗

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

Animals↗

Utility of fragmented human fetal tissue as a potential dopaminergic brain graft in Parkinson's disease.

There is increasing interest in the use of human fetal dopaminergic tissue as a source of striatal transplant in parkinsonian patients. This tissue is acquired by elective abortions. The possibilities of the use of this tissue were studied by macroscopical examination, cell-culturing followed by immunohistochemical staining and by high performance liquid chromatography. It turned out that 50% of the curettages obtained by suction abortion were too fragmented to reliably recognize the dopamine-containing area (ventral mesencephalon). Furthermore, dissection of the brainstem immediately after the abortion procedure seemed to be of utmost importance.

Brain Tissue Transplantation↗

Dextran-magnetite particles: contrast-enhanced MRI of blood-brain barrier disruption in a rat model.

Dextran-magnetite particles (DMP) were studied for their use as a MR contrast agent to visualize lesions with a blood-brain barrier (bbb) disruption. A freezing injury to the rat cerebral cortex was used as a model of bbb disruption. The biodistribution of iv-injected DMP was studied using atomic absorption spectrophotometry, electron microscopy, and MRI. One hour after injection, focal accumulation of the particles in capillary endothelial cells could be demonstrated in the freezing lesion. Despite the observation that the relaxivity of DMP in vivo appears to be less well pronounced than that in vitro, the MR imaging studies show that DMP can be used to visualize bbb disruption with adequate contrast.

Animals↗

Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.

Antibodies, Monoclonal↗

The pathogenesis of cerebral gliomatous cysts.

In this study, the authors have examined the mechanism of the formation of tumor cysts. Cyst fluid samples were obtained during surgery and by percutaneous aspiration from 22 patients with cystic cerebral gliomas. The concentration of protein was measured in the cyst fluid and blood plasma. Analysis of brain tumor cyst fluids revealed that plasma proteins constituted a major fraction (92%) of cyst fluid proteins; moreover, the protein fractions occurred in concentrations (relative to the plasma concentrations) that were around 50-fold of those in cerebrospinal fluid. This strongly indicates blood-brain barrier disruption. Evidence from computed tomographic and magnetic resonance imaging scans as well as from electron microscopy of tumor cyst walls suggests the transition of spongy edematous tissue in or around tumors into the contents of associated cysts. Pathophysiologically, blood-brain barrier breakdown is inherent to the occurrence of vasogenic brain edema. It is therefore plausible that the development of cysts is related to peritumoral vasogenic edema.

Albumins↗

Evaluation of results of temporal bone resection.

The results of 16 cases of temporal bone resection were evaluated. The resections, 12 of which were total and 4 partial, had mostly been performed for squamous cell carcinoma invading the temporal bone. Five patients in whom the intervention was considered radical and not followed by irradiation, were alive and well 9 years or more later. The significance of postoperative radiotherapy was demonstrated in 3 patients who were alive and in good health 9 years or more later, although histological examination of resection margins showed residual tumour. Eight patients died 10 months to 5 1/3 years after operation, 6 of whom from recurrence, one from radiation necrosis of the temporal lobe of the brain, and one from cerebrovascular occlusion. Histologically, squamous cell carcinoma was found significantly more among the patients who died from recurrence than among those still living.

Adult↗

Passage of DMP across a disrupted BBB in the context of antibody-mediated MR imaging of brain metastases.

To study the possible application of monoclonal antibody/dextran-magnetite conjugates in specific MR imaging of brain metastases, both components of these conjugates were tested for their ability to penetrate the endothelium during conditions of local blood-brain barrier (BBB) impairment. The passage of dextran-magnetite particles (DMP) across a disrupted blood-brain barrier was studied in a freezing lesion model using electron microscopy (EM) and MR imaging. One hour after i.v. injection, focal accumulation of DMP in capillary endothelial cells within the freezing lesion was shown by EM. In parallel with this, MR imaging indicated a strong contrast enhancement in the lesion. EM observations showed that the particles were still present in the endothelial cells four and eight hours after injection. The passage of an anti-small cell lung cancer (SCLC) monoclonal antibody across the endothelium of intracerebrally xenografted human SCLC was studied using immunohistological techniques. It was found that passage across endothelial cell occurred in the tumor within four hours after injection.

Animals↗

An improved synthesis of carbon-11 labeled acetoacetic acid and an evaluation of its potential for the investigation of cerebral pathology by positron emission tomography.

1-11C-acetoacetic acid was synthesized by carboxylation of the acetone carbanion. Purification was carried out using HPLC. The product was obtained with a radiochemical yield of up to 58%, corrected for decay, in a total preparation time of 30 min. The distribution of 1-11C-acetoacetic acid after injection into adult Wistar rats and cats was investigated by PET. When the tracer was injected into cats, 3 weeks after inflicting a unilateral freezing lesion upon the brain, accumulation of 1-11C-acetoacetic acid in the ipsilateral brain hemisphere was observed.

Acetoacetates↗

Qualitative and quantitative examination of rat and human fetal dopaminergic grafts.

This study was carried out as a prelude to possible implantations of cultured human fetal dopaminergic grafts in parkinsonian patients. Examination of fetal rat ventral mesencephalon tissue for morphology, viability, and dopamine content showed an optimal gestational age for neural grafting in rat experiments of approximately 17 days. Moreover, fetal rat ventral mesencephalon tissue was cultured, and neural dopaminergic cells were observed in cell culture in 4 (11%) out of 36 ventral mesencephalon specimens derived from 15- to 21-day-old rat fetuses. Human fetal donor material from elective abortions was examined for morphology and cell culture possibilities. In 48 curettements, fetal tissue was seen in 34 (71%) of these, resulting in 17 (50%) cultures containing dopaminergic cells. Both fetal rat and human cell cultures were continued for approximately 8 weeks and appeared to remain positive upon immunocytochemical dopamine staining.

Animals↗

Proton-nuclear magnetic resonance relaxation times in brain edema.

Proton relaxation times of protein solutions, bovine brain, and edematous feline brain tissue were studied as a function of water concentration, protein concentration, and temperature. In accordance with the fast proton exchange model for relaxation, a linear relation could be established between R1 and the inverse of the weight fraction of tissue water. This relation also applied to R2 of gray matter and of protein solutions. No straightforward relation with water content was found for R2 of white matter. Temperature-dependent studies indicated that in this case, the slow exchange model for relaxation had to be applied. The effect of macromolecules in physiological relevant concentrations on the total relaxation behavior of edematous tissue was weak. Total water content changes predominantly affected the relaxation rates. The linear relation may have high clinical potential for assessment of the status of cerebral edema on the basis of T1 and T2 readings from MR images.

Animals↗

Positron emission tomography study of 11C-acetoacetate uptake in a freezing lesion in cat brain, as correlated with 11C-tyrosine and 18F-fluorodeoxyglucose uptake, and with proton magnetic resonance imaging.

Using 11C-ACAC, 11C-TYR, and 18FDG as tracers, brain uptake of these substrates was studied in cat brain with a freezing lesion, by PET, at 1 day to 3 weeks after injury. Also MRI was conducted. Although the MRI scans depicted the morphological changes, such as edema formation, the PET studies of the brain uptake of substrates visualized the pattern of changes, which in the fresh lesion was largely governed by impairment of the BBB, but in the chronic lesion they were indicative of the proliferation of reactive cells in the process of tissue repair and edema resolution.

Acetoacetates↗

Positron emission tomographical studies of 1-11C-acetoacetate, 2-18F-fluoro-deoxy-D-glucose, and L-1-11C-tyrosine uptake by cat brain with an experimental lesion.

In cat brain with a freezing injury, the uptake of 1-11C-acetoacetate (11C-ACAC), 2-18F-fluorodeoxy-D-glucose (18FDG), and L-1-11C-tyrosine (11C-TYR) was monitored by positron emission tomography following intravenous administration of the tracers, at 1 day, and 1-3 weeks after the injury. The development and further course of the cold-induced oedema was monitored by magnetic resonance imaging. In the fresh (1 day old) lesion there was increased uptake of 11C-ACAC, probably due to release of the restrictive influence of the blood-brain barrier upon passage of the substance into brain. The uptake of 18FDG, which normally occurs by carrier-mediated transport at the barrier, was decreased in the fresh lesion, probably as a result of damage of the carrier mechanism. In the 3 week old lesion 18FDG uptake was still reduced, and 11C-ACAC uptake was still increased, although barrier function to Evans blue had recovered. It is suggested, that the increased 11C-ACAC uptake in the chronic lesion bears upon the proliferation of macrophages and reactive glial cells in the lesion. This is supported by the increased uptake of 11C-TYR in the 2 weeks old lesion, while in the fresh lesion 11C-TYR uptake was unchanged.

Acetoacetates↗

Interaction of metallic neurosurgical implants with magnetic resonance imaging at 1.5 Tesla as a cause of image distortion and of hazardous movement of the implant.

Metallic implants used in neurosurgery, comprising vascular clips, shunt valves, and metallic surgical wire for spondylodesis, induce distortion of magnetic resonance images. The image deformation usually pertains to small areas of signal suppression in its immediate vicinity, when the implant is non-ferromagnetic. The image deformation is more pronounced when the implant is ferromagnetic, but more important, as is the case with some strongly ferromagnetic aneurysm clips, the magnetic field may cause movement of the clip. Therefore, it is advisable to refrain from magnetic resonance imaging in patients harbouring intracranial aneurysm clips, as the movement in the magnetic field may be hazardous.

Animals↗

Rat striatal cation shifts reflecting hypoxic-ischemic damage can be predicted by on-line impedance measurements.

We investigated the earliest time at which irreversible damage takes place after hypoxia-ischemia in the Levine preparation of rats. In 60 rats anesthetized with chloral hydrate and maintained at one of three body temperatures, we unilaterally ligated the left common carotid artery and placed electrodes in the striatum to measure impedance (reflecting the extracellular space) during hypoxia, recovery, and/or cardiac arrest. We measured blood gases and pH at regular intervals during hypoxia in 47 rats and assessed blood-brain barrier function with Evans blue and tissue damage using Na+:K+ ratios. Shortly after hypoxia, impedance normalized in 24 rats without brain damage (normal Na+:K+ ratios, 4 hours of recovery). Sustained elevation of striatal impedance during recovery in six rats was related to an elevated Na+:K+ ratio and a disrupted blood-brain barrier. Damage was not obviously related to blood gases, pH, or the net reduction of the extracellular space during hypoxia. Hypothermia in 17 rats prevented impedance changes, and no striatal damage was found. Thus, irreversible brain damage very likely occurs during or very shortly after hypoxia. Persistent reduction of the extracellular space indicates tissue damage and can be used to monitor potential in vivo therapeutic measures.

Animals↗

Nuclear magnetic resonance relaxation in experimental brain edema: effects of water concentration, protein concentration, and temperature.

Proton relaxation times T1 and T2 of macromolecular solutions, bovine brain tissues, and experimental cat brain edema tissues were studied as a function of water concentration, protein concentration, and temperature. A linear relation was found between the inverse of the weight fraction of tissue water and the spin-lattice relaxation rate, R1, based on a fast proton exchange model for relaxation. This correlation was also found for the spin-spin relaxation rate, R2, of gray matter samples and macromolecular solutions at low concentrations. Concentrated solutions of protein-water samples showed an enhanced relaxation due to viscosity effects. The T2 of white matter was considerably lengthened with elevated water concentration, but showed no straightforward relation with the total tissue water content. The relaxation times of all samples increased with temperature, supporting the assumption of fast proton exchange in the model for relaxation. This was not found for white matter, in which T2 decreased with increasing temperature, which indicated that intermediate or even slow exchange was present. The relation found between relaxation times and tissue water content can be used to predict the amount of and/or increase in tissue water due to water-elevating processes such as edema.

Animals↗

Protective effect of fasting upon cerebral hypoxic-ischemic injury.

This study was designed to determine the effect of fasting upon cerebral hypoxic-ischemic injury. In the first part of the study the effect of fasting was determined for survival, brain tissue water and kation contents, and blood-brain barrier integrity. In the second part of the study the administration of the substrates beta-hydroxybutyrate (BHB) and glucose has been evaluated regarding their influence upon the effect of fasting. The study used the Levine-Klein model of unilateral carotid occlusion and hypoxia because it mimics clinical situations of ischemia with hypoxia. The data show that fasting did protect rats from developing brain infarction following hypoxia-ischemia. Hypoglycemia seems to be involved in the mitigation of ischemic blood-brain barrier disruption. The plasma glucose level seems to be not the only factor involved in the genesis of the tissue kation changes. Starvation-induced ketosis probably does not play a role in the protection mechanism.

Acetoacetates↗