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Biomedical subjects

M Kozak

Publications and source records attributed to M Kozak.

At least 19 recordsLinked to original sources

Structure of N6-furfurylaminopurine (kinetin) dihydrogenphosphate.

The crystal structure of kinetin dihydrogenphosphate has been determined at 115 and 293 K. Kinetin dihydrogenphosphate undergoes a polymorphic phase transition at 291.1 K. In both phases the crystal belongs to the triclinic system with the symmetry described by the space group P\bar 1. In the low-temperature phase, the unit cell is doubled along the a axis. There is a dynamic equilibrium between different tautomeric forms of the adenine residue, determined by the distribution of H atoms within the network of hydrogen bonds.

Crystallography, X-Ray↗

Lysability of arterial thrombi assessed by magnetic resonance imaging.

BACKGROUND: Intravascular thrombi change in time due to retraction and organization, which is reflected in the appearance of magnetic resonance images of clots. We have hypothesized that MRI has the potential to improve patient selection for thrombolytic treatment. The aim of our study was to analyze occlusive arterial thrombi with MRI, and to correlate the MRI parameters with the therapeutic outcome in patients with occlusive atherothrombotic disease of the superficial femoral artery who were treated with catheter-directed thrombolysis by streptokinase. PATIENTS AND METHODS: We included 13 patients with subacute (2 weeks to 3 months old) occlusive arterial thrombi and 4 patients with chronic (more than 6 months old) arterial occlusions. We measured the MRI signal intensity on gradient echo images of 98 axial slices of the subacute occlusive thrombi and in 45 slices of 4 chronic thrombi. Following MRI, the patients with subacute history were treated with catheter-directed thrombolysis. RESULTS: Thrombolysis was successful in 11/13 patients. The normalized MRI signal intensity was significantly higher in the unsuccessfully treated thrombi than in the successfully treated thrombi (1.10 +/- 0.08 vs. 0.72 +/- 0.17, p < 0.003), but the subacute and chronic thrombi did not differ in signal intensity. CONCLUSIONS: High signal intensity of arterial thrombi on gradient echo MRI might predict resistance to thrombolytic therapy.

Adult↗

Trichophyton mentagrophytes var. quinckeanum as a cause of zoophilic dermatomycosis in a human family.

Trichophyton mentagrophytes var. quinckeanum is a zoophilic form of T. mentagrophytes. It induces murine favus in the form of coarse yellow scutules bigger than 1 cm in diameter. In March, 2002, a 52-year-old male patient was examined at the Dermatology Clinic of the Medical Faculty in Kosice with a 1-week anamnesis of a solitary, oval, annular focus, 3 cm in diameter, on the right side of his face, located subauricularly. When providing the history, he has mentioned that his 12-year-old son has a ,,similar skin disease". Clinical examination of the son showed similar annular oval lesion, size about 2 x 3 cm, located in the right chest region. Since January 2002 the family has kept a guinea pig. They have obtained it through a mediator from the Kosice ZOO. The material for mycological examination was taken from peripheral parts of the foci or desquamating lesions from the father, son, and the guinea pig. Scales were examined microscopically in 20 % KOH solution with Parker's blue-black ink. The findings proved the presence of septal hyphae and formation of arthrospores. Thus, dermatomycosis was confirmed in the father and son, caused by T. mentagrophytes var. quinckeanum, the source of which was a pet guinea pig (Fig. 3, Ref. 17).

Animals↗

Studies of water penetration into LDPE--calcium lactate composite.

Penetration of water into low-density polyethylene-calcium lactate composite is studied with NMR techniques. The presence of filler speeds up the water uptake by the polymer matrix and facilitates polyethylene degradation. Spatial distribution of absorbed water molecules within the composite visualised with MRI corroborates differences in dynamical behaviour of the absorbed water molecules revealed by T2 measurements.

Absorption↗

Two polymorphs of a covalent complex between papain and a diazomethylketone inhibitor.

The three-dimensional structure of two polymorphs of a ZLFG-CH2-papain covalent complex has been determined by X-ray crystallography. The structures indicate that: (i) the methylene carbon atom of the inhibitor is covalently bound to the Sgamma atom of Cys25 of papain; (ii) the hydrophobic S2 pocket formed by Pro68, Val133, Val157, and Asp158 is occupied by the inhibitor's phenylalanyl P2 side chain; (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. Comparison with similar structures suggests that in covalent complexes preservation of main chain-main chain interactions between the enzyme and the inhibitor may have higher priority than the P-S interactions.

Binding Sites↗

Do dogs and cats present a risk of transmission of salmonellosis to humans?

Examination of rectal swabs from 187 dogs and 13 cats showed that Salmonella spp. was present in only one dog, a 4-month old mongrel puppy, weighing 3.5 kg. It was identified as S. dublin, a species specific serovar of cattle. The animal exhibited no signs of disease during clinical examination. Of the total number of examined animals this positive dog represents only 0.5%. Within the group of patients included in our monitoring in none of those with gastrointestinal problems it was possible to isolate Salmonella spp. This indicates that the risk of transmission of salmonellosis from dogs and cats in the region of Kosice seems to be rather low. On the basis of literature and our own observations we identified the potential sources and the possible ways of the transfer of this disease. The most common appears to be the oral infection by infected feed of various types, particularly by direct contamination of feed with either animal or human contaminants. In dogs and cats salmonellosis occurs most frequently in a latent form. The clinical findings vary with regard to the number of pathogens, immune status of the host, occurrence of health complications and the form of associated disease units. There are suitable isolation and diagnostic methods for diagnostics of salmonellosis. Due to the need for continuous protection of health of humans and animals, screening of occurrence of zoonotic pathogens appears topical. (Tab. 3, Fig. 1, Ref. 35.).

Animals↗

Study of the dermatophytes in dogs and the risk of human infection.

BACKGROUND: The infiltrative growth of fungi that multiplies in the tissues (dermatophytes, candida, agents of visceral mycoses) is the generally known proof of "active" functioning of these organisms. The relative importance of fungi as inducers of human and animal diseases grows constantly. METHODS: The study was carried out on dogs that showed skin changes. The frequency of examinations was determined on the basis of anamneses. Skin scrapings and affected fragile or dull hair and skin swabs were subject to Laboratory diagnostic examinations based on cultivation and microscopical examination. Our evaluations were focused on the type of parasite--ecothrix, endothrix, neoendothrix, and the size of arthrospores. RESULTS: The results of our study are presented as the incidence of dermatophytes and other micromycetes in 100 samples of skin scrapings and swabs from 100 dogs of both sexes, different breeds and age categories that had exhibited skin problems. We isolated 12 species. Malassezia pachydermatis was the most frequently detected species and was isolated from 31 cases. Trichophyton mentagrophytes was isolated from 2 samples, species Microsporum canis was isolated only from one case, Candida albicans was isolated from 3 samples. The agent Candida krusei was isolated from 5 samples, Candida pulcherrima a relatively rare candidal species, was isolated from skin of an 8-year old Dalmatian bitch, Candida sp. in 5 cases. Trichosporon cutaneum was isolated from a 3-year old Laika etc. CONCLUSION: This study confirms the need of constant research in this area. This indicates that the incidence of mycoses in dogs and other pets is of importance in the exposure of people to the risk of acquiring mycotic infections. (Tab. 1, Fig. 5, Ref. 57).

Animals↗

Study of the content of heavy metals related to environmental load in urban areas in Slovakia.

UNLABELLED: It is natural for the man to take care of his environment so the negative influences of intensification of industrial and agricultural production and the entire process of pollution are kept at minimum or eliminated as early as possible. However, they must first be identified. BACKGROUND: companion animals, for example dogs, are a very good indicator of the pollution load on the environment. They inhabit the same space as humans and are exposed to the action of the same pollutants. The most important role in contamination of the environment with heavy metals is played by emissions of different origin. For that reason it is appropriate and advantageous to evaluate the load on the man by parallel evaluation of the heavy metal load on dogs, particularly in large town agglomerations. MAIN PURPOSE: the aim of the study was to compare and evaluate the content of three heavy metals, cadmium, arsenic and lead, in the hair of dogs from two largest town agglomerations of Slovakia, Bratislava and Kosice. In addition to that, an effort was made to compare the environmental load in Bratislava and Kosice by using the dog as a bioindicator of environmental pollution with heavy metals and to quantify the content of heavy metals in dog' hair. METHODS: The generally low level of heavy metals in biological material makes it impossible to use common analytical methods. In our study the samples of dog hair were analysed using the method of atomic absorption spectrometry. The measurements were carried out on a Perkin-Elmer spectrometer, model 5000, using the following wavelengths: 228.8 nm for Cd, 193.7 nm for As and 283.3 nm for Pb. The results of analyses are presented as means. The concentrations of Cd, As and Pb are expressed in microg/kg dog hair. Statistical evaluation of results was carried out by means of Student's t-test. RESULTS: The mean values of heavy metals in the set of dogs from Bratislava reached the following levels: 38.09 microg/kg for Cd, 111.07 microg/kg for As, and 729.59 microg/kg for Pb. The set of dogs from Kosice allowed us to detect the following mean values: 22.21 microg/kg for Cd, 79.87 microg/kg for As, and 542.49 microg/kg for Pb. The mean values for the entire Slovak territory reached 27.39 microg/kg for Cd, 90.06 microg/kg for As, and 601.96 microg/kg for Pb. The comparison of the first two experimental sets of data with the Slovak mean values showed highly significant differences in arithmetic means (p < 0.01) for Cd and significant (p < 0.05) for As with the Bratislava set reaching higher values. No statistically significant differences were observed with regard to Pb. CONCLUSION: The study confirms the need for further research in this area with the dog as a bioindicator involving also other environmental loads not only that resulting from heavy metals. It indicates the importance of risk assessment in relation to environmental pollution. As the studies on animals are applicable also to the human population it appears very appropriate to use also this indirect way to point out to the negative impact of the polluted environment. Lead, cadmium and arsenic are the heavy metals that raise particular concern because of their wide-spectrum negative influences on live organisms. (Tab. 4, Fig. 5, Ref 28.)

Animals↗

Constraints on reinitiation of translation in mammals.

The efficiency of reinitiation in mammalian translation systems depends in part on the size and arrangement of upstream open reading frames (upORFs). The gradual decrease in reinitiation as an upORF is lengthened, confirmed here using a variety of sequences, might reflect time-dependent loss of protein factors required for reinitiation. Consistent with the idea that the duration of elongation is what matters, reinitiation was nearly abolished when a pseudoknot that causes a pause in elongation was inserted into a short upORF. Control experiments showed that this transient pause in elongation had little effect on the final protein yield when the pseudoknot was moved from the upORF into the main ORF. Thus, the deleterious effect of slowing elongation is limited to the reinitiation mode. Another aspect of reinitiation investigated here is whether post-termination ribosomes can scan backwards to initiate at AUG codons positioned upstream from the terminator codon. Earlier studies that raised this possibility may have been complicated by the occurrence of leaky scanning along with reinitiation. Re-examination of the question, using constructs that preclude leaky scanning, shows barely detectable reinitiation from an AUG codon positioned 4 nt upstream from the terminator codon and no detectable reinitiation from an AUG codon positioned farther upstream. These experiments carried out with synthetic transcripts help to define the circumstances under which reinitiation may be expected to occur in the growing number of natural mRNAs that deviate from the simple first AUG rule.

Animals↗

A progress report on translational control in eukaryotes.

An extraordinary amount of regulation goes into making sure that protein expression is controlled correctly. Several layers of regulation function to achieve the proper levels and proper timing of protein expression. Much is known about the protein machinery involved in translation, but we are lagging behind in understanding the mechanisms of control in eukaryotes. Kozak reviews the new second edition of Translational Control of Gene Expression, which attempts to catalog the mechanisms used by prokaryotes and eukaryotes, and the viruses that infect them and subvert their translational machinery.

Animals↗

Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping.

The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the 'open interface' of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe 'conformational disease' is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.

Amino Acid Sequence↗

Structures of two highly homologous bacterial L-asparaginases: a case of enantiomorphic space groups.

Quasi-enantiomorphic crystals of the Y25F mutant of Escherichia coli L-asparaginase and of the native Erwinia chrysanthemi L-asparaginase were obtained in the hexagonal space groups P6(5)22 and P6(1)22, respectively. The structures of these highly homologous enzymes were solved by molecular replacement and were refined with data extending to 2.2-2.5 A. These structures were compared with each other, as well as with other L-asparaginase structures previously observed with different crystal packing. It is concluded that the observed phenomenon, which is rare, was most likely to have arisen by chance.

Amino Acid Sequence↗

Expression, purification and preliminary crystallographic studies of human ketohexokinase.

Ketohexokinase (KHK; E.C. 2.7.1.3) catalyses the (reversible) phosphorylation of fructose to fructose-1-phosphate. KHK is the first enzyme in a specialized catabolic pathway metabolizing dietary fructose to the glycolytic intermediate glyceraldehyde-3-phosphate. Mutations inactivating KHK underlie the metabolic disorder essential fructosuria. The primary structure of KHK shows no significant homology to other mammalian hexokinases. It is most similar to prokaryotic ribokinases, but catalyses a distinct phosphorylation reaction. Recombinant human KHK has been crystallized in the orthorhombic form (space group P2(1)2(1)2 or P2(1)2(1)2(1)). Single crystals of this polymorph suitable for X-ray diffraction have been obtained by vapour diffusion using 2-propanol and MPD as precipitants (pH 7.5). The crystals have unit-cell parameters a = 93.4, b = 121.5, c = 108.4 A. Diffraction data were collected to 4.3 A resolution. The asymmetric unit contains four protein molecules.

Crystallization↗

Digital phased array beamforming using single-bit delta-sigma conversion with non-uniform oversampling.

Digital beamforming based on oversampled delta-sigma (delta sigma) analog-to-digital (A/D) conversion can reduce the overall cost, size, and power consumption of phased array front-end processing. The signal resampling involved in dynamic delta sigma beamforming, however, disrupts synchronization between the modulators and demodulator, causing significant degradation in the signal-to-noise ratio. As a solution to this, we have explored a new digital beamforming approach based on non-uniform oversampling delta sigma A/D conversion. Using this approach, the echo signals received by the transducer array are sampled at time instants determined by the beamforming timing and then digitized by single-bit delta sigma A/D conversion prior to the coherent beam summation. The timing information involves a non-uniform sampling scheme employing different clocks at each array channel. The delta sigma coded beamsums obtained by adding the delayed 1-bit coded RF echo signals are then processed through a decimation filter to produce final beamforming outputs. The performance and validity of the proposed beamforming approach are assessed by means of emulations using experimental raw RF data.

Journal Article↗

New strategies to prevent restenosis.

The Holy Grail of cardiovascular pharmacology has been the search for an effective therapy targeting restenosis after angioplasty and/or intra-arterial stenting. The failure of promising therapeutics in clinical trials underscores the complexity and redundancy of the signaling cascades regulating mitogenesis and fibrogenesis. Novel therapeutic modalities have potential to target dysfunctional signaling elements directly in vascular smooth muscle cells. Significant progress in the treatment against restenosis will require the exploitation and cross-fertilization of developments in the fields of pharmacology, bioengineering, genetics, and molecular biology. Collaboration among researchers in these fields will be essential.

Angioplasty↗