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Biomedical subjects

G Berencsi

Publications and source records attributed to G Berencsi.

At least 19 recordsLinked to original sources

[Transfusion-associated non-A, non-B, non-C hepatitis caused by flaviviruses].

Hepatitis C virus was shown to be a member of the flavivirus family. Tick-borne encephalitis virus and West Nile virus, members of the same family occur in Hungary, too. Serum samples from patients suffering from transfusion associated hepatitis were tested with yellow fever virus antigens for specific IgG, and IgM using immunofluorescence test. Eight hundred serum samples were tested. Yellow fever virus related IgG antibodies were found in 232 sera. In the case of 72 patients specific IgM antibodies could also be detected. The majority of the IgM positive patients underwent surgical operation and/or blood transfusion 1 to 2 months before the onset of the disease. Fifty-four sera positive for yellow fever virus-related antibodies were tested with HCV reagents, but only 13 were found to be positive, or cross-reacting. The 20 patients with yellow fever related antibodies were controlled with tick-borne encephalitis antigens, too. Nevertheless, no measurable cross-reaction could be detected. No measurable cross-reaction could be detected with the West Nile virus. The hepatitis B markers also were tested in 44 sera positive for yellow fever antibodies. There was only one, which contained HBsAg, and 10 of them proved to be positive for anti-HBcAg. The results indicate, that a non-A, non-B, non-C flavivirus is also present in the Hungarian population, which can be detected on the basis of the antigenic cross-reactivity with the attenuated yellow fever virus. This virus seems to be responsible for every 11th transfusion associated hepatitis examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Flavivirus

Multiple enlargements in the right inverted terminal repeat of the DNA of canine adenovirus type 2.

The Manhattan strain of canine adenovirus type 2 (CAV 2) was examined. Restriction endonuclease analysis and blot hybridization experiments revealed the heterogeneity of the viral DNA. At least 9 unequally expanded species of the viral genome have been recognized. This diversity is caused by different enlargements in the right inverted terminal repeat (ITR) of the virus. The differences between the individual enlargements were shown to be the different multiples of 150 base pairs. Relatedness of CAV 2 DNA to the DNA of bovine adenovirus type 2 (BAV 2) and human adenovirus type 2 (HAV 2) has also been observed during DNA hybridization experiments.

Adenoviridae

Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene.

Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenylalanine hydroxylase (PAH). Several mutations in the PAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of the PAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg243 to a termination codon, and the mutant allele is associated with haplotype 4 of the PAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.

Alleles

Characterization of an intermediate adenovirus strain.

An intermediate strain of human adenovirus of subgenus D was investigated by type specific serological reactions and restriction endonuclease analysis. The latter method showed the strain identical to the prototype strain of human adenovirus type 9 as well as did serum neutralization tests. In contrast with the previous methods haemagglutination inhibition tests showed the strain related to both the prototypes strains of human adenovirus 9 and 13.

Adenoviruses, Human

Relationship of E1 and E3 regions of human adenovirus 35 to those of human adenovirus subgroups A, C and D.

Cloned PstI fragments of human adenovirus 35 (AV35) genome were compared with the DNA of representatives of human adenovirus subgroups A (type 12), B (type 7), C (types 1, and 5), D (type 8), and E (type 4), using blot hybridization techniques. The E1b region of AV35 was found to be more distantly related to those of other subgroups than E1a regions sequences and examined by others. DNA hybridization was observed only between E1b of AV35 and the DNA of AV4, thus the recombinant constructed might be applied as B-subgroup-specific diagnostic probe. Common nucleotide sequences were detected within the E3 regions of serotypes 1, 4, 5, 7, 8, and 35. On the basis of inter-subgroup homology, and PstI-fragments it may be concluded, that the structure of E3 sequences of AV7 and AV35 DNA are closely related to those of AV3 DNA sequenced by Signäs et al. [18]. E4 regions were compared only of serotypes representing subgroups B, C, and D. These sequences were subgroup specific, similarly to E1b regions.

Adenovirus Early Proteins

Molecular cloning and physical mapping of the DNA of human adenovirus type 35.

The prototype strain of the human adenovirus type 35 (AV35) was examined. BamHI, EcoRI, HindIII, KpnI, PstI, and SalI restriction endonucleases were used for the mapping of DNA fragments. Three original maps were constructed, and previously published maps were somewhat modified. A PstI-specific fragment library was also prepared and characterized using the pBR322/E. coli system. Some of the recombinants seem to be applicable for rapid DNA diagnostics, and for the comparative mapping of type- and subgroup-specific DNA sequences. The comparative presentation of physical maps of subgroup B human adenoviruses might improve the efficiency of genotyping of adenoviruses using restriction endonucleases.

Adenoviruses, Human

The effect of prednisolone on the foetotoxicity of cadmium in pregnant mice.

The effects of prednisolone was investigated on the foetotoxicity of cadmium. CFLP female mice were given a single i.p. dose of 2.5 mg cadmium (Cd) per kg body weight on day 5 or 9 of gestation. This treatment significantly decreased both the number of live foetuses and foetal weights on day 18 of gestation. Prednisolone (0.1 mg kg-1) given daily from the day of cadmium treatment death, prevented the effects of cadmium on foetal weights in both groups, and on the number of live foetuses when cadmium was given on day 9 of gestation. When Cd was given on day 13 of gestation similar treatment with prednisolone did not influence either litter size or the weights of 1-day-old pups.

Animals

Subtypes of bovine adenovirus type 2 exhibit major differences in region E3.

The genomes of two adenovirus type 2 strains which were isolated from different hosts have been investigated. One of these strains designated ORT-111 was originally isolated from a lamb in Hungary during an outbreak of pneumoenteritis. This isolate was typed as bovine adenovirus type 2 (Ad bos 2) in a neutralization assay. The genome of ORT-111 was compared to that of the prototype strain of Ad bos 2, a virus which exclusively has been isolated from cattle. Electron microscopic heteroduplex analysis showed that 95% of the genomes were well matched, forming stable duplexes at Tm -6 degrees. Two distinct substitution loops were, however, seen which were approximately 0.5 and 1.0 kbp long. The centers of the two loops were located 5.3 and 7.7 kbp from one end of the Ad bos 2 genome. In order to map these regions relative to the gene map of human adenovirus type 2 (Ad2), restriction enzyme cleavage fragments of the two bovine viruses were cloned and hybridized to different sets of restriction fragments of human Ad2. From these results it was apparent that the centers of the two substitution loops were located at coordinates 76 and 83, respectively; thus at positions which fall within region E3 and the adjacent gene for polypeptide VIII of human Ad2. The observed differences between the genomes of the two Ad bos 2 strains are in sharp contrast to those previously observed when the genomes of different human adenovirus serotypes were compared. In the latter case the hexon and the fiber genes showed the most pronounced variation.

Adenoviridae

Changes of adenovirus hexon associated with different passage history of Ad h 1.

Two descendants of the prototype strain AD71-Washington D. C. were obtained by independent passaging for at least 18 years in Kiev, and in Budapest (Ad h 1 kappa, and Ad h 1B, respectively). By restriction endonuclease mapping, the DNA was identical corresponding to the patterns of human adenovirus type 1. In spite of this, SDS-polyacrylamide gel electrophoresis revealed that the purified hexon of Ad h 1 kappa was of lower Mr than the subunit of Ad h 1B. In contrast to this, the native capsomer (hexon) of Ad h 1 kappa exhibited lower electrophoretic mobility in agarose gel electrophoresis than the native hexon of Ad h 1B. Oligopeptide mapping of the main hexon bands from SDS-polyacrylamide gels revealed the presence of unique spots among the chymotryptic oligopeptides of Ad h 1B, too. Thus, the differences in the sensitivity to proteolytic cleavage during purification seem to have a structural basis. Antigenic analysis of the native hexon capsomers was performed using polyclonal antihexon immunsera. Immunodiffusion, immunoelectrophoresis, and competitive RIA were used for comparison. The results indicate that native hexon capsomers of Ad h 1 kappa and Ad ha 1B possess antigenic differences within the type-specific regions, nevertheless, their genetic background could not be detected by the restriction endonucleases applied. It cannot be excluded that the differences were results of altered assembly of virions under different passage conditions.

Adenoviruses, Human

Spontaneous lymphoma in an AKR mouse with dominance of 42 chromosomes.

The chromosome content of the lymphoma cells derived from various organ manifestations of an AKR female mouse with spontaneous lymphoma was investigated. It was found that the lymphoma cells were heterogeneous and the dominant subpopulation of the lymphoma cells contained 42 chromosomes. At least 8 subpopulations of the lymphoma were detected at the karyotype analysis, from which the 41XX; +15; 41XX; +18; 42XX; +15, +18 and 44XX; +5, +8, +15, +18 karyotypes were the most frequent aberrations. The frequency of the presence of various subpopulations was different also in the thymus, spleen and lymph nodes. The authors suggest that over the trisomy of chromosomes 15, other trisomies (e.g. gain of chromosome 18) can play a role in the AKR mouse lymphomagenesis.

Animals

Comparative chromosome examination of AKR mouse lymphoma after its i.p. transplantation with thymus- or spleen-derived lymphoma cells into hybrid mice.

A spontaneous AKR female mouse lymphoma was transplanted with its thymus cell suspension (10(6) cells i.p.) into AKR female mice. Lymph node cell suspension derived from one of the leukemic mice was injected (10(6) cells i.p.) into AKR females. The lymphoma cells "homing" to the thymus of one of the AKR females were suspended in Parker solution and 5 X 10(6) cells were given i.p. 5 (C3H X AKR) F3 hybrid mice (group 1). The lymphoma cells "homing" to the spleen of the same AKR female were also suspended, and 5 X 10(6) cells were injected i.p. into 5 (C3H X AKR) F3 hybrids (group 2). Chromosomes were prepared from the thymus and the spleen of two mice in both groups. The karyotypes derived from the hybrids of group 1 were compared to that of the group 2. It was found that the lymphoma cells "homing" to the thymus could be characterized by the trisomy of chromosome 15, while the lymphoma cells "homing" to the spleen had primarily the trisomy of chromosome 18. The results indicate that the thymus manifestation of the spontaneous AKR lymphoma is heterogeneous, and it contains at least two major subpopulations of the lymphoma cells.

Animals

Chromosomal aberrations and fetotoxic effects of atmospheric arsenic exposure in mice.

Fetal chromosomal damage and toxicity were investigated in mice exposed to the atmospheric concentrations of 28.5 mg m-3, 2.9 mg m-3 and 0.26 mg m-3 of arsenic for 4 h per day on the 9th, 10th, 11th and 12th days of gestation. On the 18th day, the fetuses were removed, and the following parameters were examined: the number of dead fetuses, retardation in growth, osteogenesis and chromosomal aberrations in liver cells. It was found that exposure to As2O3 at 28.5 mg m-3 caused fetotoxic effects and chromosomal damage, while the two lower exposures produced no significant changes with the exception of a slight decrease (9.9 and 3.1%, respectively) in fetal weight.

Abnormalities, Drug-Induced

The teratogenic, embryotoxic, and prenatal mutagenic effect of 3-methyl-4-nitrophenol in the mouse.

The teratogenic, embryotoxic, and prenatal mutagenic effects of 3-methyl-4-nitrophenol were investigated in CFLP strain pregnant mice treated with the compound at the dose of 3 X 25 mg/kg. After treatment on the 7th, 9th, and 11th days of pregnancy, the embryos were examined on the 18th day of pregnancy for obvious malformations and bone preparations were made with alizarin red S staining. The examination of chromosome aberrations in samples from liver cells of embryos was performed by the method of P.K. Datta, H. Rigger, and E. Schleiermacher (in Chemical Mutagenesis in Mammals and Man, F. Vogel and G. Röhrborn, eds., pp. 198-206, Springer-Verlag, Berlin/Heidelberg/New York, 1970). 3-Methyl-4-nitrophenol at the applied dosage did not result in teratogenic or prenatal chromosome damage in contrast to the damaging effect of 4,6-dinitro-o-cresol which was previously reported.

Abnormalities, Drug-Induced

A study of the mutagenic effect of 3-methyl-4-nitrophenol on the somatic cells of the mouse.

3-Methyl-4-nitrophenol is a resultant metabolite inside the organism when fenitrothion (O,O-dimethyl O-(3-methyl-4-nitrophenyl) thiophosphate)-containing pesticides undergo a chemical change due to the action of liver cell enzymes. It is also used as a basic compound for synthesis in the chemical industry. Groups of CFLP strain mice were treated ip with single doses (25 mg/kg) of this chemical in aqueous or alcoholic solution. Another group was treated ip with the same dose on ten weekly occasions. Chromosomes were prepared from the bone marrow cells 24 and 48 hr after the treatment. The results do not exclude the possibility of a mutagenic effect.

Animals

Delineation of antigenic determinants of adenovirus hexons by means of monoclonal antibodies.

60 hexon-specific mouse hybridoma clones were selected by using crystallized hexon capsomers of human adenovirus type 1 as immunizing and selecting antigen. The reactivities of the monoclonal antibodies were tested with purified hexon preparations from 10 human adenovirus types by enzyme-linked immunosorbent assay and passive hemagglutination techniques. The reactivity patterns delineated a total of 41 adenovirus-type-1-related determinants present on a number of heterologous hexons in different interspecies combinations. The pattern of interspecies specificities did not coincide with the current grouping of adenoviruses into subgenera.

Adenoviruses, Human

Reactivity of mouse ascitic fluids containing monoclonal antibodies directed against adenovirus hexon.

Thirty-two mouse hybridoma ascites were produced, containing hexon specific monoclonal antibodies, using crystallized hexons of human adenovirus type 1 as immunizing and selecting antigen. The reactivity of the ascitic fluids was tested with hexon preparations of 11 different human adenovirus species (serological types) belonging to 4 different subgenera by ELISA and passive haemagglutination (HA) methods. By these methods the 32 hybridoma antibodies showed 4 and 12 distinct reactivity patterns (type of cross-reactions) respectively. In the positive cases significant differences could be detected in the titres of the hybridoma antibodies in both ELISA and HA. It can be assumed that adenovirus type 1 hexon-related epitopes are present on a number of heterologous hexons in characteristic (interspecies) combinations for the given heterologous hexon and that a gradient of relationship may exist among the antigenic structures of hexons of the different adenovirus species.

Adenoviruses, Human