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Biomedical subjects

H Dvoráková

Publications and source records attributed to H Dvoráková.

At least 19 recordsLinked to original sources

Neoparamoeba branchiphila n. sp., and related species of the genus Neoparamoeba Page, 1987: morphological and molecular characterization of selected strains.

A total of 18 Neoparamoeba strains were characterized both morphologically and using the SSU rRNA gene sequences as molecular markers. Nine were isolated from gills of farmed Atlantic salmon, Salmo salar L., six from sediments sampled in areas of sea-cage farms and three from net material of sea-cages. The newly obtained sequences extended substantially the dataset of Neoparamoeba strains available for phylogenetic analyses, which were used to infer taxonomic relatedness among 32 strains morphologically assigned to this genus. In addition to the N. pemaquidensis and N. aestuarina clades, phylogenetic analyses clearly distinguished a third clade with sequences from six strains. Members of this clade are characterized as representatives of a new species, N. branchiphila n. sp. The diagnostic primers for the identification of this species are introduced.

Analysis of Variance↗

Somatostatin: beneficial effects on remission in young adult patients with newly diagnosed diabetes mellitus type 1.

To assess a possible influence of short-term administration of somatostatin on remission development in adult patients with newly diagnosed diabetes mellitus type 1, the somatostatin analog octreotide was given for two weeks after the establishment of the diagnosis at the daily dose of 150 microg subcutaneously in addition to the regular insulin and metabolic therapy. When compared to the control group, the remission was achieved earlier in the octreotide group (6+/-4 weeks vs. 11+/-12 weeks in the control group, p 0.05) and its duration was longer (99+/-49 weeks vs. 49+/-31 weeks in the control group, p 0.05). Moreover, remission also appeared in patients from the octreotide group with lower endogenous residual secretion of insulin (basal C peptide at the time of diagnosis in patients who later entered remission was 0.23+/-0.16 nmol/l vs. 0.34+/-.18 nmol/l in the control group, p<0.05). The increase of 24-h urine excretion of C-peptide after the therapy with octreotide was predictive for remission development. It can thus be concluded that octreotide administration in adults with newly diagnosed diabetes mellitus type 1 positively influences both the onset and duration of remission.

Adult↗

Synthesis and cytostatic activity of substituted 6-phenylpurine bases and nucleosides: application of the Suzuki-Miyaura cross-coupling reactions of 6-chloropurine derivatives with phenylboronic acids.

The Suzuki-Miyaura reaction of protected 6-chloropurine and 2-amino-6-chloropurine bases and nucleosides with substituted phenylboronic acids led to the corresponding protected 6-(substituted phenyl)purine derivatives 6-9. Their deprotection yielded a series of substituted 6-phenylpurine bases and nucleosides 10-13. Significant cytostatic activity (IC(50) 0.25-20 micromol/L) in CCRF-CEM, HeLa, and L1210 cell lines was found for several 6-(4-X-substituted phenyl)purine ribonucleosides 12 (X = H, F, Cl, and OR), while the 6-phenylpurine and 2-amino-6-phenylpurine bases 10 and 11, as well as 2-amino-6-phenylpurine ribosides 13, were entirely inactive against these cell lines.

Animals↗

Towards regioselective synthesis of oligosaccharides by use of alpha-glucosidases with different substrate specificity.

alpha-Glucosidase from two microbial sources, Bacillus stearothermophilus and Brewer's yeast, has been used to catalyze transglycosylation reactions and a comparative study was carried out to determine the regioselectivity of this reaction. Bacterial alpha-glucosidase exhibited higher transfer activity with maltose and was able to synthesize tri- and tetrasaccharides in high yield (27%). In the case of yeast enzyme, only trisaccharides were synthesized in lower yield. Structure analysis of transglycosylation products by means of GC-MS and NMR spectroscopy revealed a correlation between the hydrolytic substrate specificity and the regioselectivity of transglycosylation reaction. Higher substrate specificity of bacterial enzyme, however, influenced its transglucosylation activity toward other saccharide acceptors.

Chromatography, High Pressure Liquid↗

Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base.

A series of dialkyl esters of purine and pyrimidine N-[2-(phosphonomethoxy)ethyl] derivatives substituted at position 2, 6, or 8 of the purine base or position 2, 4, or 5 of the pyrimidine base were prepared by alkylation of the appropriate heterocyclic base with 2-chloroethoxymethylphosphonate diester in the presence of sodium hydride, cesium carbonate, or 1,8-diazabicyclo[5,4, 0]undec-7-ene (DBU) in dimethylformamide. Additional derivatives were obtained by the transformations of the bases in the suitably modified intermediates bearing reactive functions at the base moiety. The diesters were converted to the corresponding monoesters by sodium azide treatment, while the free acids were obtained from the diester by successive treatment with bromotrimethylsilane and hydrolysis. None of the PME derivatives in the pyrimidine series, their 6-aza or 3-deaza analogues, exhibited any activity against DNA viruses or retroviruses tested, except for the 5-bromocytosine derivative. Substitution of the adenine ring in PMEA at position 2 by Cl, F, or OH group decreased the activity against all DNA viruses tested. PMEDAP was highly active against HSV-1, HSV-2, and VZV in the concentration range (EC50) of 0.07-2 microg/mL. Also the 2-amino-6-chloropurine derivative was strongly active (EC50 = 0.1-0. 4 microg/mL) against herpes simplex viruses and (EC50 = 0.006-0.3 microg/mL) against CMV and VZV. PMEG was the most active compound of the whole series against DNA viruses (EC50 approximately 0.01-0.02 microg/mL), though it exhibited significant toxicity against the host cells. The base-modified compounds did not show any appreciable activity against DNA viruses except for 7-deazaPMEA (IC50 approximately 7.5 microg/mL) against HIV-1 and MSV. The neutral (diisopropyl, diisooctyl) diesters of PMEA were active against CMV and VZV, while the corresponding monoesters were inactive. The diisopropyl ester of the 2-chloroadenine analogue of PMEA showed substantially (10-100x) higher activity against CMV and VZV than the parent phosphonate. Also, the diisopropyl and diisooctyl ester of PMEDAP inhibited CMV and VZV, but esterification of the phosphonate residue did not improve the activity against either MSV or HIV.

Animals↗

[Importance of short-term administration of low doses of somatostatin analog in the development and remission of type 1 diabetes mellitus in adult patients].

The objective of the presented work was to evaluate the short-term administration of octreotide on the development, onset and persistence of remission in recent insulin-dependent diabetics. The importance of remission means for the patient a clinically favourable condition with satisfactory metabolic compensation and a greater metabolic stability during the subsequent course of the disease. The period of remission is important from the aspect of prevention of late organ complications. Two-week treatment with octreotide, 150 micrograms/day, administered during the first month after establishment of the diagnosis was not associated with serious undesirable effects. Treatment with octreotide led to more frequent development of remission, partial and complete, as compared with a control group. In the majority of diabetics in the intervened group remission started immediately after administration of octreotide. The serum value of peptide-C as part of the glucagon test made at the time of diagnosis had a predictive value for the development of induced and spontaneous remission. Octreotide administration increased the probable development of remission even in patients with a substantially lower peptide C value at the time of diagnosis as compared with controls. The preliminary results indicate also a protraction of the remission period.

Adult↗

Acyclic nucleotide analogs derived from 8-azapurines: synthesis and antiviral activity.

Reaction of phosphoroorganic synthons with 8-azaadenine, 8-aza-2, 6-diaminopurine, and 8-azaguanine using cesium carbonate yielded regioisomeric 8-azapurine N7-, N8-, and N9-(2-(phosphonomethoxy)alkyl) derivatives. This reaction followed by deprotection afforded isomeric 2-(phosphonomethoxy)ethyl (PME), (S)-(3-hydroxy-2-(phosphonomethoxy)propyl) [(S)-HPMP], (S)-(3-flouro-2-(phosphonomethoxy)propyl) [(S)-FPMP], (S)-(2-(phosphonomethoxy)propyl) [(S)-PMP], and (R)-(2-(phosphonomethoxy)propyl) [(R)-PMP] derivatives. 13C NMR spectra were used for structural assignment of the regioisomers. None of the 8-isomers exhibited any antiviral activity against herpesviruses, Moloney murine sarcoma virus (MSV), and/or HIV. 9-(S)-HPMP-8-azaadenine (23) and PME-8-azaguanine (65) were active against HSV-1, HSV-2, and CMV at 0.2-7 micrograms/mL, VZV at 0.04-0.4 microgram/mL, and MSV (at 0.3-0.6 microgram/mL). PME-8-azaguanine (65) and (R)-PMP-8-azaguanine (71a) protected MT-4 and CEM cells against HIV-1- and HIV-2-induced cytopathicity at a concentration of approximately 2 micrograms/mL.

3T3 Cells↗

Synthesis of 2'-aminomethyl derivatives of N-(2-(phosphonomethoxy)ethyl) nucleotide analogues as potential antiviral agents.

A series of purine and pyrimidine N-(2-(phosphonomethoxy)ethyl) derivatives bearing aminomethyl, (dimethylamino)methyl, morpholinomethyl, and (trimethylammonio)methyl groups at the 2'-position were synthesized. The compounds were prepared by alkylation of the heterocyclic bases with appropriately substituted (aminoalkyl)oxiranes followed by condensation of the resulting intermediates with dialkyl ((p-tolylsulfonyl)oxy)methanephosphonate and subsequent treatment of the obtained diester with bromotrimethylsilane. 9-(3-Amino-2-(phosphonomethoxy)propyl)adenine (2a) proved active against varicella zoster virus (VZV), cytomegalovirus (CMV), and Moloney murine sarcoma virus (MSV) in the concentration range of 7-35 micrograms/mL. None of the other aminoalkyl derivatives demonstrated significant antiviral activity against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), VZV, (CMV), vaccinia virus (VV), MSV, and human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2).

3T3 Cells↗

Antiviral activity of selected acyclic nucleoside analogues against human herpesvirus 6.

Human herpesvirus 6 (HHV-6) was examined in vitro for its sensitivity to a broad range of nucleoside analogues, including acyclovir (ACV), ganciclovir (GCV), penciclovir (PCV), buciclovir (BCV), brivudin (BVDU), the N7-isomer of 6-deoxyganciclovir (S2242), foscarnet (phosphonoformic acid, PFA), and several acyclic nucleoside phosphonate (ANP) analogues such as (S)-HPMPA, (S)-HPMPC, PMEA and PMEDAP. Antiviral efficacy was monitored microscopically by the inhibitory effect of the compounds on HHV-6-induced cytopathic effect in human T-lymphoblastoid HSB-2 cells. In addition, a newly developed immunofluorescence/flow cytometric assay (FACS) was used to determine HHV-6-specific antigen expression. A close correlation was observed between the antiviral data obtained by the microscopic assay and the flow cytometric assay. Marked antiviral efficacy was noted for S2242, PFA and the ANP analogues (S)-HPMPA, (S)-HPMPC, (S)-cHPMPC, (S)-3-deaza-HPMPA, (S)-3-deaza-cHPMPA, (S)-HPMPG and (R)-HPMPG. Also, PMEA and PMEDAP proved highly active against HHV-6 infection, whereas (S)-FPMPA and (R)-PMPDAP were inactive. ACV was only slightly protective against HHV-6, and no activity was found for GCV, PCV, BCV and BVDU. Overall, the efficacy of the nucleoside analogues against HHV-6 appeared to correlate with their efficacy against human cytomegalovirus (HCMV).

Adenine↗

An adapted program of colorectal cancer screening--7 years experience and cost-benefit analysis.

The Czech program of colorectal cancer screening differs from most foreign programs in a number of points. The age interval of screened population was limited to 45 to 60 years. Screening was multicentric, with one reference center. More than 95% of the subjects screened were asymptomatic employees of various factories, boards and institutions. Total colonoscopy was the primary procedure in all Haemoccult-positive subjects. Some 109,213 subjects received 3 Haemoccult slides. Compliance was 83.1%, and Haemoccult was positive in 2.92% of the subjects. The diagnostic program revealed 347 (13.1%) cancers, 763 adenomas in 592 (22.2%) subjects, and other bleeding conditions in 1043 (39.2%) persons. Dukes A or B colorectal cancer was found in two-thirds of the screened subjects and in only one-third of non-screened symptomatic patients. Average diagnostic and therapeutic costs were almost the same in both groups. Gross national product savings realized by one asymptomatic subject were 315,540 Czechoslovak Crowns (approximately 18,560 US-dollars at the 1989 exchange rates). The adapted program was found to be effective, and its use in a population with a high incidence of colorectal neoplasia deserves consideration.

Adenocarcinoma↗

[Costs and benefits of screening for colorectal tumors using the Hemoccult test in asymptomatic individuals 45-60 years of age].

Screening of colorectal tumours by the Haemoccult test (HT) in asymptomatic subjects aged 45-60 years makes it possible to assess the diagnosis of colorectal carcinoma (CR-CA) in two-thirds of the affected subjects in Dukes stage A and B, as compared with one third of symptomatic patients of the same age group. The mean diagnostic and therapeutic costs related to the relative incidence of individual stages of Dukes staging of CR-CA in screened asymptomatic individuals and symptomatic patients are approximately equal. The analysis is not concerned with costs of care after surgical and supplementary treatment which are considerable in subjects with the advanced form of the disease. Its incidence is significantly higher in symptomatic patients. The mean expected productive age under 60 years is in symptomatic patients 2.604 years and in asymptomatic individuals 4.357 years. The mean national product assembled during this period is 468.720 Kcs and 784.260 Kcs resp. The difference in favour of one asymptomatic subject in the analyzed group is 38,495.880 Kcs. These facts fully justify further extension of screening programmes of CR-CA in our population.

Colorectal Neoplasms↗

[Techniques of endoscopic treatment of malignant colorectal adenomas with respect to the subsequent prognosis of the patients].

Since 1981 we detected in 45 patients (28 men, 17 women) 31 adenomas with severe dysplasia (ATD; formerly intramucous carcinoma) and 22 invasive carcinomas in the adenoma (IK penetrating beneath the muscularis mucosae). 95% of all findings were in the left colon before the lienal flexure. Patients with ATD were subjected only to endoscopic operation; of 22 of the subjects with IK 15 were recommended for surgery, and endoscopic treatment alone was provided to seven patients. Forty subjects were followed up on a long-term basis (on average for 34 months). Of 23 patients with ATD one female patient died from ischaemic heart disease, the remainder survive without signs of colorectal carcinoma. Of 17 subjects with IK followed up on a long-term basis five died (all after surgery as a result of generalization of the disease). All 7 patients with IK who had only endoscopic treatment survive without signs of relapse of the disease. In patients with ATD the authors consider EP as the definite therapeutic method, if it is feasible from the technical aspect. Patients with ATD and IK who were subjected to EP are checked after 6 weeks. A total coloscopic check-up is made subsequently in subjects with IK during the first year twice a year and in later years once a year, in subjects with ATD after annual intervals for a period of 5-6 years.

Adenoma↗

Long-term yersiniosis surveillance project in Czechoslovakia.

The paper presents an epidemiological analysis of 8,232 cases of yersiniosis caused by Y. enterocolitica 03 over 1972-1988 as reported by Hygienic Stations. The steady epidemiological characteristics of yersiniosis were the prevalence of children and boys and a typical seasonal pattern with differences between the Czech and Slovak Republics. In the Czech Republic, there were several incidence peaks following, when summarized, the incidence curve of other alimentary infections, whereas in the Slovak Republic morbidity reached its peak during winter months. The numbers of isolated strains oscillated significantly between districts and by years. It appears that the number of positive findings in different districts is not only an objective value reflecting a mosaic-like pattern of incidence but also depends on the quality of microbiological diagnostics.

Adolescent↗

[Expression of CA 19-9 in tubular and tubulovillous adenomas of the descending and sigmoid colon and the rectum with respect to morphologic differentiation characteristics and the adenoma-carcinoma sequence].

Expression of CA19-9 was studied in 29 adenomas and 6 adenocarcinomas of the distal colon in rectum. The authors did not find an unequivocal correlation between expression of CA19-9 and the morphological differentiation. Expression of CA19-9 was recorded twice in epithelia of normal mucosa.

Adenocarcinoma↗

Absence of cytomegalovirus, Epstein-Barr virus, and papillomavirus DNA from adenoma and adenocarcinoma of the colon.

Biopsy specimens from 13 patients with adenocarcinoma of the colon and from 10 patients with endoscopic polypectomies for colon adenoma were examined for the presence of the DNA of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) types 2, 6, 16 and 18. The specific activities of viral DNA probes obtained by nick--translation ranged from 10(7) to 10(8) cpm/micrograms DNA. By Southern blot hybridization with an estimated sensitivity of 10 pg virus DNA which corresponded to 0.05 virus genome equivalents per cell we failed to detect any virus DNA in the biopsy material tested.

Adenocarcinoma↗

Fluorescent analogs of acyclic S-adenosyl-L-homocysteinase inhibitors.

Fluorescent analogs of S-adenosyl-L-homocysteinase inhibitors derived from acyclic nucleoside series have been synthetized by alkylation of heterocyclic bases with appropriate synthons, or by modification of preformed adenine derivatives. None of the newly prepared compounds derived from 2-aminopurine, lin-benzoadenine or 1,6-ethenoadenine significantly inhibited the above enzyme.

Adenosine↗