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Biomedical subjects

J Hanus

Publications and source records attributed to J Hanus.

At least 19 recordsLinked to original sources

[Tools and methods of developing educational programs in medical biophysics].

In this work various types of programs which can be used in a learning and teaching process are analysed. Also the procedure of creating software for CAL is studied and the procedure, that is the most suitable one for developing CAL is suggested here. Also recommended properties of software for teaching and learning medical biophysics are described. General characteristics and types of authoring tools are discussed in this work and a set of authoring tools is described in more details. Conclusions are documented and demonstrated by program Blood Circulation. For development of this program the authoring system Authorware 3.5 was selected. The program is organized as a hypertext with possibility to find words, with a list of the last visited pages, and with an on line help system. This program works with a text, graphics, interactive animated schemes and with interactive equations. In the program it is possible to test the level of knowledge by means of solving problems or multiply choice test.

Biophysics↗

[Use of thermoelectric properties of materials with shape memory in medicine].

Article deals with some possibilities of the combination of the shape memory and another physical properties of nitinol (Ti-Ni alloy) for application in the medicine. The thermoelectric properties of originally developed miniature thermocouple probe with the shape memory are described in details. The shape memory effect of the thermocouple is based on the use of the combination of the metals nitinol and constantan.

Alloys↗

Cytokinin-derived cyclin-dependent kinase inhibitors: synthesis and cdc2 inhibitory activity of olomoucine and related compounds.

Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpur ine), and other N6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34cdc2/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G1/S and G2/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.

Animals↗

Induction of apoptosis and regression of spontaneous dog melanoma following in vivo application of synthetic cyclin-dependent kinase inhibitor olomoucine.

This case report describes a dog with spontaneous melanoma of the orofacial region which was treated by a synthetic inhibitor of cyclin-dependent kinases, i.e. olomoucine (OC). The drug was applied i.v. in a single dose of 8 mg/kg/day for 7 days in succession. Repeated bioptic examinations of metastatic cervical lymph nodes showed rapid induction of apoptosis in tumor cells as early as on the third day of treatment. Standard clinical and laboratory examinations did not reveal side effects of the therapy. There were no detectable manifestations of myelosuppression, hepatotoxicity, nephrotoxicity or neurotoxicity. However, transient anemia developed following bleeding from a devitalized tumor mass. For this reason, the dog underwent surgery to minimize tumor load as well as to eliminate the source of bleeding. Two kilograms of primary tumor were extirpated in the course of surgery, including cervical node metastases. Unfortunately, the dog died soon after surgery due to respiratory depression. Histological examinations of the tumor tissue showed marked apoptosis of melanoma cells in both the primary tumor and metastases. The induction of programmed cell death of cancer cells by OC resulted in rapid eradication of at least 68% of the tumor cells. The remaining melanoma cells retained at least equally well in vitro sensitivity to OC as to drugs currently used in clinical practice.

Animals↗

Photoaffinity labelling of the mitochondrial uncoupling protein by [3H]azido fatty acid affects the anion channel.

Brown adipose tissue (BAT) mitochondria were incubated with the azido derivative of fatty acid (hexadecanoic) containing four tritium atoms, [3H]AzHA, and among all mitochondrial proteins only a few proteins were photolabelled after irradiation with UV. It suggests the existence of specific fatty acid binding sites on mitochondrial proteins. It was also possible to label with [3H]AzHA the isolated uncoupling protein (UcP) of BAT mitochondria with a low stoichiometry--lower than one AzHA per dimeric UcP. These results together with the observed competition (i.e. prevention of photolabelling) of various UcP anionic substrates with [3H]AzHA and its dodecanoic acid analogue, suggest the existence of the specific fatty acid binding site on UcP identical with the anion channel or anion translocating site.

Adipose Tissue, Brown↗

Photoactivated azido fatty acid irreversibly inhibits anion and proton transport through the mitochondrial uncoupling protein.

The protonophoretic function of uncoupling protein (UCP) is activated by fatty acids. According to the "docking site" hypothesis (Jezek, P., and Garlid, K. D., J. Biol. Chem. 265, 19303-19311, 1990), the fatty acid binding site is identical with the anion channel of UCP. Skulachev (Skulachev, V. P. (1991) FEBS Lett. 294, 158-162) extended this hypothesis by suggesting that fatty acid anions are transported by UCP and that H+ are delivered by back-diffusion of the protonated fatty acid through the lipid bilayer. In this model, UCP does not transport H+ at all but rather enables fatty acids to act as cycling protonophores. New evidence supports this mechanism (Garlid, K. D., Orosz, D. E., Modriansky, M., Vassanelli, S., and Jezek, P. (1996) J. Biol. Chem. 271, 2615-2620). To help elucidate these hypotheses, we synthesized a photoreactive analog of dodecanoic acid, 12-(4-azido-2-nitrophenylamino)dodecanoic acid (AzDA), and studied its effect on transport in mitochondria and proteoliposomes. AzDA behaved in every respect like a typical fatty acid. In micromolar doses, AzDA activated H+ translocation and inhibited Cl- and hexanesulfonate uniport through UCP. After UV light exposure, however, activation of H+ transport was inhibited, whereas inhibition of anion transport was preserved. These effects were irreversible. Photolabeling of mitochondria with [3H]AzDA resulted in a prominent 32 kDa band of UCP, and few other proteins were labeled. The results indicate that AzDA can be ligated to the protein at or near the docking site, causing irreversible inhibition of both H+ and anion transport. The finding that fatty acid-induced H+ transport disappears along with anion transport supports the fatty acid-protonophore mechanism of H+ transport by UCP.

Adipose Tissue, Brown↗

The multithermocouple for the use in radiothermotherapy.

The original multithermocouple probe developed for the use in radiothermotherapy is described in this article. On the basis of experimental measurements and theoretical assumptions the properties of the probe are exactly defined and the mathematical model of the probe is given and identified.

Hyperthermia, Induced↗

In vitro release of hydrocortisone from topical preparations and automated procedure.

The in vitro drug release profile of hydrocortisone (HC) from creams, ointments, and lotions has been determined using an automated procedure. A diffusion cell system and commercially available synthetic membranes were utilized for the studies. The use of a synthetic membrane obviates the problems associated with using skin membranes. Uniform creams and ointment samples for determining release rate profile were prepared by using the teflon mask. Automated sampling avoids operator artifacts. The automated technique developed for determining the in vitro release rate profile of the drug from creams, ointments, and lotions using a diffusion-cell system appears to be a reasonable and practical procedure for assuring batch-to-batch uniformity of topical drug products.

Administration, Topical↗

Computer-aided three-dimensional reconstructions of biological objects using simple facilities.

An analysis of serial sections is an important method applied in all fields of biology studying objects divided into sections, especially at light and electron microscopy levels. It affords a qualitative and quantitative information on spatial organization of tissues, cells and organelles. This study describes simple and cheap ways of obtaining computer-aided three-dimensional reconstructions of biological objects from serial sections.

Computer Graphics↗

Use of the adaptive classifier for determination of LD50 in the acute radiation disease.

In experiments on female Wistar rats a new method for the determination of LD50 is demonstrated and compared with the classical probit method using the same experimental animals. The method is applicable for the computation of LD50 and analogical quantities in man, too. The method is based on the application of an adaptive logical circuit (ADALINE) trained for the dichotomous prognostic classification of irradiated individuals quod vitam according to a set of clinical and laboratory indicators registered on the third day after irradiation. After the training procedure has been finished, the classifier makes possible an individual prognosis of survival or death. The analogue output signal according to which the classification is performed changes continually from negative to positive values and exhibits S-shaped relation to the radiation dose. Its zero value corresponds to the position of LD50 on the abscissa. For the construction of the searched function, i.e. for the optimum approximation of experimentally obtained values of the output signal, the method of the changeable polyhedron was applied belonging to the optimalization numerical methods used in the regulation technics. The computed value of LD50 was 7.80 Gy in rats very closely corresponding with the value 7.61 Gy determined by means of the classical probit method.

Acute Disease↗