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Biomedical subjects

M Dvorák

Publications and source records attributed to M Dvorák.

At least 19 recordsLinked to original sources
PubMed2001

Biodistribution and antitumour efficacy of long-circulating N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in nude mice.

The aim of this study was to evaluate the influence of the molecular weight (mol. wt) of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (DOX) conjugates (P-DOX) on biodistribution and therapeutic efficacy in nu/nu mice bearing human ovarian carcinoma OVCAR-3 xenografts. Copolymerisation of HPMA, a polymerisable derivative of DOX (N-methacryloylglycylphenylalanylleucylglycyl doxorubicin) and a newly designed crosslinking agent, N(2),N(5)-bis(N-methacryloylglycylphenylalanyl-leucylglycyl)ornithine methyl ester monomers resulted in novel, high mol. wt, branched, water-soluble P-DOX containing lysosomally degradable oligopeptide sequences as crosslinks and side-chains terminated in DOX. Four conjugates with mol. wt of 22, 160, 895 and 1230 kDa were prepared. The results indicated that the half-life in blood and the elimination rate from the tumour were up to 28 times longer and 25 times slower, respectively, for P-DOX (mol. wt=1230 kDa) than for free DOX. Treatment with P-DOX (mol. wt > or = 160 kDa) inhibited tumour growth more efficiently than that of 22 kDa P-DOX or free DOX (P<0.02) at a 2.2 mg/kg DOX equivalent dose. In conclusion, the administration of long circulating P-DOX resulted in enhanced tumour accumulation with a concomitant increase in therapeutic efficacy.

Animals↗
PubMed1999

High-molecular weight HPMA copolymer-adriamycin conjugates.

High-molecular weight (branched) water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing lysosomally degradable oligopeptide crosslinks were synthesized by radical copolymerization of HPMA and newly designed crosslinking agents, N(2), N(5)-bis(N-methacryloylglycylphenylalanylleucylglycyl)ornithine s with different modification of the carboxy group. The length of the primary chain was controlled by the addition of a chain transfer agent, 3-mercaptopropionic acid. A polymerizable derivative of the anticancer drug adriamycin (ADR), N-methacryloylglycylphenylalanylleucylglycyl adriamycin, was added to some polymerization mixtures. This resulted in high-molecular weight, branched, water-soluble HPMA copolymers containing oligopeptide sequences in the crosslinks as well as in side-chains terminated in ADR. The degradability of the crosslinks as well as the release of ADR by lysosomal enzymes isolated from rat liver were investigated.

3-Mercaptopropionic Acid↗
PubMed1999

Myb-interacting protein, ATBF1, represses transcriptional activity of Myb oncoprotein.

Using the yeast two-hybrid system, the transcription factor ATBF1 was identified as v-Myb- and c-Myb-binding protein. Deletion mutagenesis revealed amino acids 2484-2520 in human ATBF1 and 279-300 in v-Myb as regions required for in vitro binding of both proteins. Further experiments identified leucines Leu325 and Leu332 of the Myb leucine zipper motif as additional amino acid residues important for efficient ATBF1-Myb interaction in vitro. In co-transfection experiments, the full-length ATBF1 was found to form in vivo complexes with v-Myb and inhibit v-Myb transcriptional activity. Both ATBF1 2484-2520 and Myb 279-300 regions were required for the inhibitory effect. Finally, the chicken ATBF1 was identified, showing high degree of amino acid sequence homology with human and murine proteins. Our data reveal Myb proteins as the first ATBF1 partners detected so far and identify amino acids 279-300 in v-Myb as a novel protein-protein interaction interface through which Myb transcriptional activity can be regulated.

Amino Acid Sequence↗
PubMed1999

The "small" polydisperse cytoplasmic extrachromosomal DNA of chicken leukaemic myeloblasts and the avian myeloblastosis virus core-bound DNA seem to descend from origin regions of chromosomal DNA replication.

Nucleotide sequences are presented for 12, 7 and 12 cloned extrachromosomal DNAs by nature harbored in nucleoprotein (NP) complexes forming chicken leukaemic myeloblast (CHLM) post microsomal sediment (POMS) components A, B and C, respectively, and for 11 cloned avian myeloblastosis virus (AMV) DNAs. Analysis of the abundance of sequence motifs significant for eukaryotic chromosomal DNA replication origin (ori) regions (and their initiation zones) has shown that these DNAs are reminiscent of cell DNA fragments enriched in ori sequences (Rao et al., 1990) and/or sequence features of several eukaryotic chromosomal oris containing clusters of modular sequence elements (Dobbs et al., 1994). Accordingly, these DNAs, with an (A + T) content prevalently higher than that of the total cell DNA, revealed the presence of asymmetrically distributed (A + T)-rich stretches, scaffold attachment region (SAR) T consensuses, polypyrimidine nucleotide (poly(Py)) tracts and minimal Saccharomyces cerevisiae autonomously replicating sequence (ARS) consensus, in abundance comparable with that of these sequences of DNA fragments enriched in oris. All these DNAs were found to be enriched also in sequence elements held as primase (Pr) attachment sites. Moreover, DNAs of POMS component B and those of AMV DNA were found to be enriched in the asymmetric pyrimidine (Py) heptanucleotide motif of Waltz et al. (1996) occurring in the initiation zones of ori region. Consequently, these extrachromosomal DNAs, portion of which represents a precursor of AMV DNA, seem to descent from initiation zones of various ori regions of an early replicating chromosomal myeloblast DNA. In addition, a possible explanation of the inclination of these DNAs to form multimers is presented.

Animals↗
PubMed1999

[Diagnosis and treatment of pancreatic islet cell tumors producing vasoactive intestinal polypeptide (VIPoma)].

The incidence of VIPoma is approximately one per 10 million population. Thus in the Czech Republic this rare disease should be diagnosed once per year. The authors present their experience with the diagnosis and treatment of patient born in 1956, who suffered since 1990 from diarrhoea, at first episodically. In 1992-1994 the diarrhoea was profuse, caused dehydration, hypokalaemia and severe metabolic acidosis without an increase of the anion gap. As a result of dehydration the patient developed acute renal insufficiency. Due to hypokalaemia he developed paroxysmal atrial fibrillation. The diagnosis was based on the clinical finding and later confirmed on laboratory examination by a high VIP serum concentration. For treatment of diarrhoea Sandostatin was used. The tumour was located only after a scan with 123I-VIP in the cauda of the pancreas. Scintigraphy with labelled octreotide, similarly as other imaging methods (sono, X-ray and CT) were not effective. In 1994 left-sided hemipancreatectomy was performed. Although the patient was operated four years after the onset of the disease, no secondaries were detected. After surgery the diarrhoea stopped and no further treatment was necessary.

Humans↗
PubMed1999

[Pregnancy after kidney transplantation].

In the period 1966-1997 renal allografting was performed in 1746 recipients, 244 of whom were women in fertile age. In 32 of them 45 pregnancies were registered. 29 of them (64%) resulted in abortion, which was spontaneous in 4 and medically advised in 25. There were 16 labours, 4 of them free of any complications; of the latter, hypertension was the most frequent one (8). Of the former, 13 were solved by caesarean section and 3 were vaginal deliveries. Of 15 live babies 7 were immature (one died 1.5 year later of renal failure due to microcystic kidneys). No unfavourable effect of pregnancy on prognosis and on long-term graft function was found.

Adult↗
PubMed1997

The Myb leucine zipper is essential for leukemogenicity of the v-Myb protein.

The AMV v-Myb oncoprotein causes oncogenic transformation of myelomonocytic cells in vivo and in vitro. Its transforming capacity is strictly dependent upon the N-terminal DNA binding domain, the central transactivation region, and on the C-terminal domain containing a putative leucine zipper motif. Here we show that the v-MybL3,4A mutant, in which Leu325 and Leu332 of the leucine zipper have been replaced by alanines, failed to induce leukemia in virus infected chicken. This demonstrates that the leucine zipper domain is indispensable for v-myb induced leukemogenesis in vivo. v-MybL3,4A was, however, still able to transform myelomonocytic cells from chicken bone marrow in vitro. Yet, while v-mybL3,4A transformed cells were impaired in growth at 37 degrees C, they failed to grow at 42 degrees C, the physiological body temperature of avian species. This might explain the loss of v-MybL3,4A leukemogenic potential in vivo. We also demonstrate that the v-Myb leucine zipper domain interacts in vitro with two host cell proteins, p26 and p28. This interaction is compromised in v-MybL3,4A indicating that binding of v-Myb to p26 and p28 might be important for the leukemogenic potential of v-Myb.

Amino Acid Sequence↗
PubMed1996

[Treatment of duodenal ulcer with pantoprazole. A multicenter study].

BACKGROUND: The inhibition of H+/K(+)-ATPase (proton pump) of gastric parietal cells by substituted benzimidazoles represents a new therapeutic approach in conditions connected with hypersecretion of hydrochloric acid. Pantoprazol is the newest member of this group of drugs. Monotherapy of duodenal ulcer with pantoprazole or ranitidine was evaluated in terms of healing rate, tolerance and compliance. METHODS AND RESULTS: A double-blind, parallel-group comparing study (double dummy technique) of treatment florid duodenal ulcer (diameter 5-20 mm) was performed in 95 subjects (age 18-74 years). The active substances were either pantoprazole (40 mg before breakfast-47 subjects) or ranitidine (300 mg before bedtime-48 subjects). The average diameter of the ulcer and subjective complaints before treatment were comparable in both groups. After 2 weeks of pantoprazole therapy 88.5% of ulcers (a) and 87.2% patients (b) were cured, whereas the corresponding values in the ranitidine series amounted to 66% (a) and 62.5% (b) only (p = 0.006 for both (a) and (b)). The rate of healing in relative values of reducing the ulcer size was significantly higher after 2 weeks of pantoprazole therapy (p = 0.026 (a) and 0.0027 (b)). All ulcers healed after 4 weeks of this regimen. The difference between the pantoprazole and ranitidine series after 4 weeks was closely above the 5% level of significance (p = 0.589 for (a) and 0.0588 for (b) respectively). This was due to the low number of patients in both groups at this time interval, particularly in the pantoprazole group. Pain during day-time and regurgitation were observed significantly more frequently after ranitidine therapy. The compliance was very good and practically no adverse effects of pantoprazole therapy were observed. CONCLUSIONS: The healing rate of duodenal ulcer with pantoprazole monotherapy (40 mg before breakfast) was significantly higher than with ranitidine (300 mg before bedtime). The compliance of patients and the tolerance of pantoprazole were very good and its administration was not associated with any side-effects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Avian stem cell factor (SCF): production and characterization of the recombinant His-tagged SCF of chicken and its neutralizing antibody.

Recombinant chicken stem cell factor (SCF) was produced in bacteria as a histidine-tagged protein (His delta SCF) and purified by affinity chromatography on an Ni(2+)-NTA agarose column. His delta SCF is devoid of signal peptide and transmembrane domains and therefore mimics a soluble form of SCF. We demonstrate that the factor is biologically fully active in supporting sustained proliferation of SCF-dependent red blood progenitor cells of chicken in vitro. Polyclonal SCF-specific antibodies were raised in rabbits and shown to display potent SCF-neutralizing activity. Thus, recombinant chicken His delta SCF together with the SCF-specific antibody provide valuable tools for studying the role of SCF and c-kit receptor in development, growth and differentiation of avian haematopoietic cells.

Amino Acid Sequence↗
PubMed1995

Characterization of human, mouse and rabbit anti-gliadin antibodies by ELISA and western blotting.

Monoclonal, hyperimmune rabbit and human serum anti-gliadin antibodies were analyzed by ELISA and immunoblotting techniques. In Western blotting the difference in reactivity between monoclonal and human antibodies was quantitative rather than qualitative. Rabbit antisera differed in reactivity according to the protein used for immunization. The rabbits immunized by the peptic-tryptic pancreatic digest of gliadin reacted similarly to the patients. In ELISA, significantly higher reactivity with crude, A-, glyc-gli, alpha-, beta- and omega-gliadins was found in the patients' sera than in controls.

Animals↗
PubMed1993

Identification of CpG island at the 5' end of murine leukemia inhibitory factor gene.

We identified a CpG island at the 5' end of murine leukemia inhibitory factor gene (LIF). The CpG island is 0.6 kb long and covers most of the first exon and first intron. The region is non-methylated, its G+C content is 65% and relative frequency of CpG dinucleotide is 0.7. The block of 150 nucleotides, which is 72% conserved between murine, human, ovine and porcine genes, is a part of the CpG island. Two DNA fragments from this CpG island interact with nuclear proteins from NIH 3T3 cells. One fragment partially covers the block of conserved nucleotides. Human, ovine and porcine LIF genes also contain G+C- and CpG-rich sequences in the corresponding region.

Animals↗
PubMed1993

[Endoscopic ultrasonography of the upper part of the digestive tract. II].

Endoscopic ultrasonography is a new method of visualization which makes it possible to visualize reliably and in detail the wall the digestive tract and its close surroundings. Indication is above all diagnosis of tumours and their staging. The authors submit their initial experience with the method in a group of 71 examinations in 65 subjects. The conclusions of endosonography were confirmed as correct in 96.7% and provide evidence of the asset and possibilities of the method in the differential diagnosis of diseases of the upper portion of the digestive tract.

Endoscopy, Digestive System↗
PubMed1993

Avian myeloblastosis virus core-bound 7 S DNA, a collection of minute replicative host-cell DNA structures.

The early replicative nature of avian myeloblastosis virus core-bound 7 S DNA (AMV DNA), indicated by our preceding findings (Ríman et al., 1993), has been confirmed using various experimental approaches. It has been shown by agarose and polyacrylamide gel electrophoresis that this DNA represents actually a collection of molecules the size of which is strongly reminiscent of the minute early replicative structures found in DNA of sea urchin embryos (Baldari et al., 1978). With such a characteristic correspond, the sequence properties of the individual AMV DNA clones, the majority of which were found to be AT-rich with ARS-like motifs and stretches of A-residues carrying conformational requirements for bending. In comparative hybridization experiments, AMV DNA exhibited the highest homology with chicken leukaemic myeloblast scaffold-bound DNA. Compatible with high replicative activity of AMV DNA was also found its specific [methyl-3H]thymidine radioactivity. The constancy of the virus content of this DNA and its virus age-dependent cleavage changes taking place inside the virus core structure open the question of possible significance of this special host DNA for the reaction machinery represented by the retroviral nucleoprotein core complex.

Animals↗
PubMed1993

The carboxy-terminal domain of c-Myb activates reporter gene expression in yeast.

We have shown previously that c-myb expressed in the yeast S. cerevisiae mediated efficient transcriptional activation of reporter genes designed with specific Myb Recognition Elements (MRE's), confirming that this proto-oncogene is able to function as a regulator of transcription in that heterologous context. Here we show that in yeast, as in higher eucaryotic cells, the central domain of c-Myb displays transactivating capacity. In yeast, however, the carboxy-terminal region, defined as a negative regulatory domain in higher cells, activates transcription as well and appears to be a more potent transactivating domain than the central domain itself. Within this region two domains, namely C1 and C2, have been defined that contribute about equally to the activity of the carboxy-terminal region. C1 spans the sequences missing in AMV v-myb while C2, which contains the leucine-zipper motif is specifically absent in the E26 v-myb in addition to C1. The c-Myb DNA-binding domain itself has no effect on the level of transcription in yeast. We also show that AMV v-Myb stimulates gene expression in yeast with about half the efficiency of full length c-Myb. The fact that the carboxy-terminal region either stimulates or inhibits transactivation properties of c-Myb, depending on the cellular context, stresses the participation of putative c-Myb partner proteins in Myb regulated processes and reopens the question of whether the oncogenic activation of c-myb is indeed due to the increased transactivation capacity of its onco derivatives.

Amino Acid Sequence↗
PubMed1992

Production of v-Myb and c-Myb in insect cells infected with recombinant baculoviruses.

Recombinant baculoviruses expressing the v-myb and c-myb genes in infected insect cells were constructed. The electrophoretic mobilities of their immunoreactive products were the same as those of the authentic Myb proteins from chicken cells. The system provides a convenient source of relatively large amounts of v-Myb or c-Myb for in vitro binding studies.

Animals↗
PubMed1992

[Sonographic findings in Crohn's disease].

In 59 subjects (25 men and 34 women) with confirmed Crohn's disease 91 sonographic examinations were made, using dynamic records by means of a sector probe with a frequency of 3.5 and 5 MHz. The disease had persisted on average for 7.1 years. A positive sonographic finding was recorded in 68% of the examined subjects, incl. 42% where the finding on palpation of the abdominal cavity was negative. During examination the following typical findings were recorded: the symptom of a tubular structure with a thickened intestinal wall (frequency 77.5%), cockade symptom (65%), convolution of the loops (62.5%), congestion in the intestinal loops (10%) and abscess in the abdominal cavity (7.5%). Ultrasonography is a significant diagnostic method which can help in the differential diagnosis of resistance on palpation and in the follow up of the disease and the effect of therapy in patients with Crohn's disease.

Crohn Disease↗
PubMed1992

[Endoscopic ultrasonography of the upper digestive tract].

Endoscopic ultrasonography is a useful combination of endoscopy and abdominal ultrasonography. It visualized in detail the wall of the digestive tract and is thus indicated for the diagnosis of pathological processes of the wall and its close surroundings, in particular the differential diagnosis of tumours, assessment of their size and operability. The method has become available also under our conditions. The present paper deals with its technique and informative value.

Digestive System↗