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Biomedical subjects

R Braun

Publications and source records attributed to R Braun.

At least 19 recordsLinked to original sources

Evolution of the retrotransposons TRS/ingi and of the tubulin genes in trypanosomes.

The African trypanosomes have genomes of high plasticity, as demonstrated for instance by their ability to shuffle their genes around, coding for variant-specific surface glycoproteins (VSGs). Another indication of their genome plasticity is the presence of multiple retro-elements. The retrotransposon-like element TRS/ingi is present in many copies in the genome of trypanosomes. One particular derivative of TRS/ingi, called TUBIS, had previously been found to interrupt a tubulin gene in a particular strain of T. brucei. Here both TRS/ingi and TUBIS were studied by hybridizing genomic DNA of various strains and species of trypanosomes with suitable probes in order to elucidate the evolution of this family of retro-elements. The TSR/ingi elements are highly repeated and have very long open reading frames, while TUBIS clearly is a truncated, inactivated form of this element, found in only one particular chromosomal location. Both elements were shown to be present in several strains and species of the subgenus Trypanozoon, in particular in T. brucei brucei, T. gambiense, T. rhodesiense, T. equiperdum and T. evansi. They could not be detected in species of other subgenera, in particular in T. congolense and T. cruzi. These findings suggest that the retrotransposon TRS/ingi was acquired by trypanosomes only after divergence of present day subgenera. The TUBIS element was found in exactly the same chromosomal location (at the 3' end of the tubulin gene cluster) in many different strains and species of the subgenus Trypanozoon. This shows that the element was transposed to this location before speciation of the subgenus. Although, TRS/ingi is unlikely to be involved directly in VSG switching, it may have contributed to the genome plasticity of trypanosomes.

Animals

Detection of 6-thioguanine-resistant spleen lymphocytes in different mouse strains by autoradiography.

The variant frequencies for 6-thioguanine-resistant spleen cells in different mouse strains have been estimated by autoradiography for animals without chemical treatment and in cases of in vivo mutagen dosage with ethylnitrosourea and cyclophosphamide, respectively. In untreated mice, the following variant frequencies have been found: C57Bl/6J, 2.84 x 10(-5);NMRI, 3.04 x 10(-5);DBA/2J, 5.91 x 10(-5). The selective concentration of 6-thioguanine was 100 microM for strains NMRI and DBA, while in the case of C57Bl with this concentration, no variant cells could be counted and a selective concentration of 50 microM was chosen. Treatment with 70, 140, and 210 mg/kg ethylnitrosourea resulted in increased variant frequencies in cells isolated 8 or 15 days later. On the other hand, doses of 20, 60, and 120 mg/kg cyclophosphamide did not result in a clear dose-response relationship of variant frequency in cells isolated 1, 8, 15, 22, and 29 days after treatment. These data are discussed with respect to findings in human populations exposed occupationally to cyclophosphamide.

Animals

Antigenic epitopes of NEF proteins from different HIV-1 strains as recognized by sera from patients with manifest and latent HIV infection.

Human immunodeficiency virus (HIV) infection that generally causes a strong antibody response toward HIV may sometimes occur in a latent form, characterized by seronegativity in assays based on structural HIV proteins. Latently infected individuals, however, often have an antibody response against the nonstructural regulatory HIV-1 protein NEF, a factor implicated in down-regulation of viral expression. In order to define the specificity of NEF antibodies, we looked for antibody response against more than 600 overlapping nonapeptides representing the total NEF sequence of three different HIV-1 isolates BRU, SF2, and MAL. Nine distinct homologous antigenic epitopes were recognized by sera from seropositive HIV-1-infected individuals by the peptide ELISA. We further demonstrated that sera from "at risk" individuals, with no antibodies to HIV structural proteins but reacting with the recombinant NEF protein in Western blot, recognize the same epitopes. Immunological assays based on the defined NEF epitopes can therefore be used to diagnose early or latent HIV Infection.

Amino Acid Sequence

Increased frequency of 6-thioguanine-resistant lymphocytes in peripheral blood of workers employed in cyclophosphamide production.

The frequency of 6-thioguanine-resistant peripheral blood lymphocytes has been determined by autoradiography in a control population and a population of cyclophosphamide-exposed individuals. The mean variant frequency in a non-exposed population was found to be 2.76 +/- 1.48 X 10(-5). Subpopulations of smokers and non-smokers revealed statistically significant differences in the variant frequencies, i.e. 3.52 +/- 1.55 X 10(-5) and 2.07 +/- 1.05 X 10(-5) respectively. In 20 out of a total of 23 individuals employed in cyclophosphamide synthesis and manufacturing, the variant frequency of 6-thioguanine-resistant lymphocytes was found to be higher than the maximum individual frequency found in the control population. The mean variant frequency in the cyclophosphamide-exposed population was 13.64 +/- 13.56 X 10(-5), a statistically significant increase as compared to the mean control frequency. There was no correlation between variant frequency and duration of employment suggesting that this test reflects the actual exposure and not a cumulative effect.

Adult

[Changes in sex behavior caused by fear of AIDS--an empirical study of male heterosexual and homosexual students].

UNLABELLED: This study examines changes in sexual behaviour in the context of the fear of being infected with the HI-Virus and, in particular, considers the influence of a relationship and of sexual orientation. The population studied included 72 homosexual and 54 heterosexual male students. RESULTS: (1) Only 7% of the heterosexuals, but 68% of the homosexuals report changes in their sexual behaviour pattern. (2) Among the homosexual group practice-oriented alterations (avoiding oral and anal sex or using condoms for these practices) and relationship-oriented alterations (reducing the number of sex partners) occur likewise. (3) Practice-oriented changes are less frequent among homosexuals with partners than those without. (4) Those homosexuals questioned who are in conflict with their homosexuality have less confidence in potential sex partners. They are more inclined to have "monogamous" relationships.

Acquired Immunodeficiency Syndrome

Effects of naftidrofuryl on the indocyanine green clearance and cardiovascular function of rats with liver cirrhosis.

The influence of intrahepatically infused naftidrofuryl (Dusodril) on indocyanine green (ICG) clearance was measured in healthy rats and rats with liver cirrhosis. In control rats naftidrofuryl reduced the ICG clearance from 0.043 to 0.029 mumol/min/g liver. Plasma half-life of ICG was prolonged significantly from 3.07 to 4.25 min. This was probably due to a depression of the cardiovascular function (blood pressure, heart-rate). In cirrhotic rats, the removal rate of ICG (0.050 mumol/min/g liver) was significantly lower and its half-life (7.61 min) longer than in normal rats. Probably the extraction rate for ICG was so low that naftidrofuryl did not further impair the reduced ICG clearance and half-life inspite of reduced diastolic blood pressure and heart rate.

Animals

Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer.

By Western blot technique, 519 samples of human sera were tested for the presence of antibodies to the human papillomavirus (HPV) type 16 proteins E4 and E7 that had been expressed in Escherichia coli as fusion proteins. Sera were obtained from patients attending the University hospitals for reasons unrelated to HPV infections (controls), from patients with HPV-associated lesions, as well as from patients suffering from cervical cancer. Within the control population, 18.1% of them had antibodies that reacted with the E4 protein, and 3.9% of them had antibodies that reacted with the E7 protein. No sex-specific difference in the antibody prevalence was observed. The highest proportion of anti-E4 antibody-positive individuals (40.7%) was observed in the age group between 11 and 20 years. The frequency of anti-E4-positive sera was threefold higher in patients with HPV-associated genital lesions than that in age-matched controls. Antibodies against the HPV16 E7 protein were found 14 times more frequently in patients with cervical cancer, compared with age- and sex-matched controls (P less than .00001). From these data, we concluded that anti-E4 antibodies may be correlated with virus replication and that anti-E7 antibodies may represent a marker for cervical cancer development.

Adolescent

The tubulin gene cluster of Trypanosoma brucei starts with an intact beta-gene and ends with a truncated beta-gene interrupted by a retrotransposon-like sequence.

In Trypanosoma brucei the genes coding for alpha- and beta-tubulin are arranged in a single cluster comprising about ten alternating alpha and beta genes. The cluster starts at its 5' end with an intact beta gene. In this area, a 1.1-kb segment upstream of the mini-exon addition site has been sequenced. Several potential transcription signals were seen. The 3' end of the cluster terminates in the middle of a beta gene, making it an inactive truncated pseudogene. The adjoining 1.7-kb sequence shows a high degree of similarity with a retrotransposon-like (RTnL) element previously characterized elsewhere in the trypanosome genome. This is the first report of an RTnL element interrupting a protein-coding gene of T. brucei.

Animals

[Demarcation of diseases].

Feinstein's opinion that diseases overlap does not stand up to professional criticism. Different diseases can certainly present very similarly, but they cannot overlap, in the same way as specialties cannot overlap. The specialties are separated from each other according to their different connections with the diseases. Diseases are separated from each other by their relations to the symptoms and clinical signs on the one hand and the results of medical consultation on the other hand. These considerations emphasize the fact that doctors should not make a diagnosis too hastily if a typical symptomatology is present. That, however, has nothing to do with overlapping of diseases, but with the temptation in the presence of a typical clinical picture to jump to a diagnosis without first having scrupulously clarified the possibility that the classical symptomatology was not, in fact, really due to the atypical manifestations of a totally different disease.

Appendicitis

[Surgery of pleomorphic adenoma of the parotid gland].

In literature opinion is divided, whether for treatment of pleomorphic adenoma in the parotid gland partial parotidectomy is adequate or complete parotidectomy is necessary. In a retrospective analysis of 123 complete parotidectomies in pleomorphic adenomas the macroscopic tumor extension was compared with the microscopic findings. Additionally 35 pleomorphic adenomas were examined in histological serial sections. The retrospective analysis showed in 6%, the serial sections in 11% microscopic tumor in the macroscopic tumorfree inner lobe. A clinical follow-up examination of 85 patients operated by complete parotidectomy because pleomorphic adenoma resulted in a relapse-quota of 3.5%. The function of the facial nerve was in most cases normal, in 8.2% a weakness of the mandibular branch was found. These results indicate that the risk to leave tumor can be reduced evidently by a complete parotidectomy.

Adenoma, Pleomorphic

[Microbial mutagenicity testing of N-nitrosoiminostilbene and N-nitrosoiminodibenzyl, the nitrosation products of the drugs carbamazepine and trimipramine hydrochloride].

The active agents of the drugs Finlepsin and Herphonal, carbamazepine and trimipramine, were nitrosated under simulated human gastric conditions. For both formed N-nitroso compounds, N-nitroso iminostilbene (N-nitroso-5H-dibenz(b,f)azepine) and N-nitroso iminodibenzyl (N-nitroso-10,11-dihydro-5H-dibenz(b,f)azepine), tests for mutagenic potency in the Ames-test gave negative results.

Carbamazepine

Mutagenicity of antiviral substances of nucleobase analogue type in Salmonella typhimurium employing metabolic activation by mouse liver homogenate or cell-free plant extracts.

Five nucleobase analogues with antiviral properties were tested for their mutagenic activity in his mutant strains TA 1535, TA 1537, TA 1538, TA98, and TA 100 of S. typhimurium by means of preincubation tests with and without metabolic activation by cell free fractions from mouse liver (S-9) and maize seedlings (S-14). In one bacterial strain 6-azathymine increased the revertant counts in the absence of metabolic activation systems. In the presence of S-9 mix, the same substance became mutagenic for another tester strain. Metabolic activation by S-14 resulted in weak mutagenicity of 5-azadihydrouracil in high concentrations. 6-Azauracil, 5-azauracil, and 5-azadihydro-1,3-diacetyluracil were without mutagenic activity in all Salmonella-strains used. Cyclophosphamide, like other standard promutagens, was shown to become mutagenic in the presence of S-14 plant fraction. Thus S-14 activation system besides the S-9 liver system can be employed in mutagenicity testing with microbial systems.

Animals

Mutagenicity assay with Salmonella typhimurium revealing biotransformation of antiphytoviral substances by cell-free plant extract.

The mutagenic activity of four antiphytoviral substances was tested in reversion mutagenicity assays with a set of histidine auxotrophic strains of Salmonella typhimurium by means of the preincubation method. A possible metabolic activation of the substances by cell free fractions from maize seedlings (S-14-fraction) and for comparison from mouse liver (S-9 mix) was examined. None of the guanidine, phenyl urea and thiadiazole compounds exerted mutagenic activity in the bacterial strains in experiments without metabolic activation. Cyanoguanidine and N-phenyl-N-carboxyphenylurea became mutagenic for Salmonella strain TA98 after metabolic activation by the S-14 plant fraction. Both substances were not mutagenic in the presence of S-9 mix made from mouse liver. The promutagen cyclophosphamide proved highly mutagenic in experiments with S-14 mediated plant metabolic activation. This kind of bacterial mutagenicity assay is valuable in investigations of potential agrochemicals, as the examples have shown.

Animals

Benzene-derived free radical--a possible mediator of its carcinogenicity. I. Ultrastructural and functional studies on the effect of benzene on human white blood cells and its possible prevention.

The assumption that benzene exerts its leukemogenic action on cell components after being converted to a transient and relatively stable free radical is supported by the in vitro effect of benzene on the ultrastructure of human peripheral blood polymorphonuclear (PMN) cells, lymphocytes and monocytes. The effect was examined with a transmission and scanning electron microscope and was found to affect both the internal and external architecture of PMN cells and monocytes in a dose-dependent manner. No effect was observed on lymphocytes. Benzene did not affect the phagocytic activity of PMN cells or monocytes. Preincubation with 2-aminoethylthiosulfuric acid, a free radical scavenger, prevented the observed effects of benzene.

Benzene