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Biomedical subjects

I Otto

Publications and source records attributed to I Otto.

12 recordsLinked to original sources

[Radioiodine therapy for combined disseminated and nodular thyroid autonomy. Results after using a correction term for the disseminated part].

AIM: In combined focal and disseminated thyroid autonomy a variety of concepts in the treatment with radioiodine are used. The difference lies mainly in the calculation of the autonomous volume. This retrospective study shows a new method of calculating the autonomous volume. PATIENTS AND METHODS: In 398 patients with combined thyroid autonomy and good correlation of scintigraphically hot nodules and lesions defined by ultrasound the volume of the nodules is ascertained from scintigraphic and ultrasound parameters and the volume of the disseminated autonomous tissue is assessed with a weighting factor (VF). This factor is the ratio of impulse density in a ROI over the disseminated volume divided by the corresponding impulse density over the nodular volume of the thyroid scintigraphy. The sum of nodular volume and weighted perinodular volume gives the total autonomous volume. A standard radioiodine test gives the maximum iodine-131-uptake and effective half-life to calculate the activity to obtain a treatment dose of 400 Gy. RESULTS: The rate of success with and without thyrostatic medication was 97% with an 18.6% rate of hypothyroidism observed from 4 months post therapy onwards. CONCLUSION: The use of the weighting factor VF in the treatment of combined autonomy leads to an excellent rate of success in patients with good correlation of functional imaging and ultrasound findings.

Humans↗

Pulsatile drug-delivery systems.

Delivery systems with a pulsatile-release pattern are receiving increasing interest for the development of drugs for which conventional controlled drug-release systems with a continuous release are not ideal. These drugs often have a high first-pass effect or special chronopharmacological needs. A pulsatile-release profile is characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Pulsatile drug-delivery systems can be classified into site-specific systems in which the drug is released at the desired site within the intestinal tract (e.g., the colon), or time-controlled devices in which the drug is released after a well-defined time period. Site-controlled release is usually controlled by environmental factors, like the pH or enzymes present in the intestinal tract, whereas the drug release from time-controlled systems is controlled primarily by the delivery system and, ideally, not by the environment. This review covers various single- and multiple-unit oral pulsatile drug-delivery systems with an emphasis on time-controlled drug-release systems.

Administration, Oral↗

Neural network models of cortical functions based on the computational properties of the cerebral cortex.

We describe a biologically plausible modelling framework based on the architectural and processing characteristics of the cerebral cortex. Its key feature is a multicellular processing unit (cortical column) reflecting the modular nature of cortical organization and function. In this framework, we describe a neural network model organization and function. In this framework, we describe a neural network model of the neuronal circuits of the cerebral cortex that learn different functions associated with different parts of the cortex: 1) visual integration for invariant pattern recognition, performed by a cooperation between temporal and parietal areas; 2) visual-to-motor transformation for 3D arm reaching movements, performed by parietal and motor areas; and 3) temporal integration and storage of sensorimotor programs, performed by networks linking the prefrontal cortex to associative sensory and motor areas. The architecture of the network is inspired from the features of the architecture of cortical pathways involved in these functions. We propose two rules which describe neural processing and plasticity in the network. The first rule (adaptive tuning if gating) is an analog of operant conditioning and permits to learn to anticipate an action. The second rule (adaptive timing) is based on a bistable state of activity and permits to learn temporally separate events forming a behavioral sequence.

Cerebral Cortex↗

Visuomotor transformations underlying arm movements toward visual targets: a neural network model of cerebral cortical operations.

We propose a biologically realistic neural network that computes coordinate transformations for the command of arm reaching movements in 3-D space. This model is consistent with anatomical and physiological data on the cortical areas involved in the command of these movements. Studies of the neuronal activity in the motor (Georgopoulos et al., 1986; Schwartz et al., 1988; Caminiti et al., 1990a) and premotor (Caminiti et al., 1990b, 1991) cortices of behaving monkeys have shown that the activity of individual arm-related neurons is broadly tuned around a preferred direction of movements in 3-D space. Recent data demonstrate that in both frontal areas (Caminiti et al., 1990a,b, 1991) these cell preferred directions rotate with the initial position of the arm. Furthermore, the rotation of the population of preferred directions precisely corresponds to the rotation of the arm in space. The neural network model computes the motor command by combining the visual information about movement trajectory with the kinesthetic information concerning the orientation of the arm in space. The appropriate combination, learned by the network from spontaneous movement, can be approximated by a bilinear operation that can be interpreted as a projection of the visual information on a reference frame that rotates with the arm. This bilinear combination implies that neural circuits converging on a single neuron in the motor and premotor cortices can learn and generalize the appropriate command in a 2-D subspace but not in the whole 3-D space. However, the uniform distribution of cell preferred directions in these frontal areas can explain the computation of the correct solution by a population of cortical neurons. The model is consistent with the existing neurophysiological data and predicts how visual and somatic information can be combined in the different processing steps of the visuomotor transformation subserving visual reaching.

Animals↗

The low density lipoprotein and low density lipoprotein receptors and their possible importance in the pathogenesis of atherosclerosis.

In man and in experimental animals, elevations in plasma cholesterol lead to premature atherosclerosis. It is likely that the cholesterol-rich low density lipoprotein (LDL) plays a keyrole in atherogenesis. LDL accumulates in patients with familial hypercholesterolemia (FH), a genetic syndrome associated with a defective LDL receptor in parenchymal cells and premature atherosclerosis. Monocytic/macrophage-like cells invading the vessel wall are becoming enriched with cholesteryl ester and concentrating in the early atherosclerotic lesion. Modification of LDL stimulates the uptake of cholesterol by macrophages in vitro leading to the conversion of the cells to lipid laden foam cells. Because of this phenomenon recent investigations were focussing on the lipid metabolism of macrophages. In vitro studies have demonstrated that macrophages have specific cell surface receptors for modified forms of LDL. It was suggested that these scavenger receptors could mediate foam cell formation in vivo, too. In vivo analysis by sequential scintiscans revealed that the liver is accumulating most actively modified LDL, possibly acting as a sieve for atherogenic lipoproteins. The putative liver receptor for modified (= atherogenic) LDL was characterized as a membrane protein of 220 000 to 250 000 D by ligand blotting.

Acetylation↗

A simple and rapid anti-ligand enzyme immunoassay for visualization of low-density lipoprotein membrane receptors.

Triton X-114 was used to solubilize the membrane proteins of bovine adrenal cortex and human leukocytes. The solubilized membrane proteins were subjected to electrophoresis and transblotted to nitrocellulose paper and incubated with LDL/acetyl-LDL. The combination of peroxidase-conjugated second antibody and 4-chloronaphthol/H2O2 allowed rapid development of colored bands where LDL or acetyl-LDL bound to electroblotted proteins. The ELISA is highly sensitive and efficient for screening a large number of samples and avoids the need for a continuous supply of radiolabeled antibodies and autoradiography.

Adrenal Cortex↗

Smoking influences the atherogenic potential of low-density lipoprotein.

The possible influence of smoking on the low-density lipoprotein (LDL) and its biological activity was investigated. Plasma LDL was prepared from healthy male smokers and nonsmokers, and oxidized with Cu (II) as prooxidant. Oxidized LDL from smokers generated significantly more lipid peroxidation products, so-called thiobarbituric acid reactive substances (TBARS), when compared to oxidized nonsmoker LDL. Analysis of vitamin E levels in LDL obtained from both smokers and nonsmokers revealed that the vitamin E content of smoker LDL was significantly less than that of nonsmoker LDL. The amounts of cholesteryl esters formed in cultured P388. D.1 macrophages were greater in the presence of smoker LDL than with nonsmoker LDL. The data suggest that some of the proatherogenic effects of smoking may be related to oxidative modification of LDL and alteration of its biological activity.

Adult↗