Robust relational parsing over biomedical literature: extracting inhibit relations.

We describe the design of a robust parser for identifying and extracting biomolecular relations from the biomedical literature. Separate automata over distinct syntactic domains were developed for extraction of nominal-based relational information versus verbal-based relations. This allowed us to optimize the grammars separately for each module, regardless of any specific relation resulting in significantly better performance. A unique feature of this system is the use of text-based anaphora resolution to enhance the results of argument binding in relational extraction. We demonstrate the performance of our system on inhibition-relations, and present our initial results measured against an annotated text used as a gold standard for evaluation purposes. The results represent a significant improvement over previously published results on extracting such relations from Medline: Precision was 90%, Recall 57%, and Partial Recall 22%. These results demonstrate the effectiveness of a corpus-based linguistic approach to information extraction over Medline.

Automatic extraction of acronym-meaning pairs from MEDLINE databases.

Acronyms are widely used in biomedical and other technical texts. Understanding their meaning constitutes an important problem in the automatic extraction and mining of information from text. Here we present a system called ACROMED that is part of a set of Information Extraction tools designed for processing and extracting information from abstracts in the Medline database. In this paper, we present the results of two strategies for finding the long forms for acronyms in biomedical texts. These strategies differ from previous automated acronym extraction methods by being tuned to the complex phrase structures of the biomedical lexicon and by incorporating shallow parsing of the text into the acronym recognition algorithm. The performance of our system was tested with several data sets obtaining a performance of 72 % recall with 97 % precision. These results are found to be better for biomedical texts than the performance of other acronym extraction systems designed for unrestricted text.

[Importance of cytogenetic analysis in patients with azoospermia or severe oligozoospermia undergoing in vitro fertilization]. / Znaczenie badan cytogenetycznych u pacjentów z azoospermia lub ciezka postacia oligozoospermii, korzystajacych z zaplodnienia in vitro.

The karyotypic analysis was performed to assess the importance of genetic factor in male infertility. For that purpose, chromosomal analysis in blood lymphocytes was performed in 28 males, candidates for ICSI with azoospermia or severe oligozoospermia and in their spouses. Although chromosomal aberrations were identified in as many as 11 couples, (in 6 couples aberrations were identified in male, in 4 other couples in female partner, whereas in 1 one couple they were detected in both partners) their risk for potential offspring is unequal. Balanced autosomal aberrations detected in two males (7%) constitute a high risk since they can cause not only infertility but also severe somatic abnormalities if transferred as the unbalanced ones to the next generation. The remaining 9 chromosomal aberrations identified in this study were present in mosaic additional cell lines with low representation. In 8 of them sex chromosomes and in 1 an autosom were involved. Although these mosaic chromosomal aberrations can lower efficiency of in vitro fertilisation, the probability that they can be transferred to the next generation causing somatic abnormalities is not high. This study indicates that in case of azoospermia or severe oligozoospermia, the karyotypic analysis should be performed in both partners prior to in vitro fertilisation.

Isolation and characterization of a near-haploid human cell line.

Mammalian somatic cells are usually diploid. Occasional rare human tumors have been shown to have a hypodiploid karyotype. We have isolated a near-haploid subclone (P1-55) from a heterogeneous human leukemia cell line, KBM-7. These near-haploid cells have approximately half the human diploid DNA content and have a haploid karyotype except for a disomy of chromosome 8 (25, XY, +8, Ph(+)). This cell line maintains a majority of cells with a near-haploid karyotype for at least 12 weeks in culture. By serial subcloning, we have isolated near-haploid subclones that maintain ploidy for at least 8 months in culture. Near-haploid cells can also be efficiently isolated from mixed ploidy cultures by size selection. The availability of this human near-haploid cell line should facilitate the genetic analysis of cultured human cells.

Adaptive response and dose-response plateaus for initiation in a state-vector model of carcinogenesis.

PURPOSE: To investigate whether it is possible to explain dose-response plateaus for in-vitro X-ray irradiation of different cell lines with radioprotective mechanisms such as radiologically induced expression of scavengers and repair enzymes. MATERIALS AND METHODS: A biomathematical model was developed based on a previous state-vector model. New features of the model are a mathematical description of enhanced repair and radical scavenging as a result of irradiation. RESULTS: The model produces a plateau in the dose-response for in-vitro tranformations between 0.5 and 1 Gy and for chromosome aberrations and it predicts an inverse-fractionation effect within a selected range of doses. CONCLUSIONS: Adaptive response mechanisms within a state-vector model provide a coherent explanation of the dose-response characteristics for in-vitro transformations and chromosomal aberrations. These results suggest the need for new experimental studies described in the paper.

Incomplete masculinisation of XX subjects carrying the SRY gene on an inactive X chromosome.

46,XX subjects carrying the testis determining SRY gene usually have a completely male phenotype. In this study, five very rare cases of SRY carrying subjects (two XX males and three XX true hermaphrodites) with various degrees of incomplete masculinisation were analysed in order to elucidate the cause of sexual ambiguity despite the presence of the SRY gene. PCR amplification of 20 Y chromosome specific sequences showed the Yp fragment to be much longer in XX males than in true hermaphrodites. FISH analysis combined with RBG banding of metaphase chromosomes of four patients showed that in all three true hermaphrodites and in one XX male the Yp fragment was translocated onto a late replicating inactive X chromosome in over 90% of their blood lymphocytes. However, in a control classical XX male with no ambiguous features, the Yp fragment (significantly shorter than in the XX male with sexual ambiguity and only slightly longer than in XX hermaphrodites) was translocated onto the active X chromosome in over 90% of cells. These studies strongly indicate that inactivation on the X chromosome spreading into a translocated Yp fragment could be the major mechanism causing a sexually ambiguous phenotype in XX (SRY+) subjects.

Deletion mapping of interval 6 of the human Y chromosome.

DNAs of four individuals demonstrating abnormalities in sexual development and mosaic 45,XO/46,XY karyotypes with terminal deletions of Yq were studied using a number of Y-specific probes. The results of these analyses allowed us to map several known DNA fragments within deletion interval 6 in the following order: Ycen-pDP105B/52dA, 50f2E, Fr25-II/Fr15-II, 50f2C, 49f-Yqter (groups of fragments in undetermined order separated by diagonal lines).

Increased frequency of chromatid breaks in lymphocytes of heterozygotes of ataxia telangiectasia after in vitro treatment with caffeine.

The frequencies of caffeine-induced chromosomal aberrations (CA), mainly chromatid (CdB) and chromosome (CB) breaks, were studied in lymphocyte cultures derived from 6 obligatory heterozygotes and 1 homozygote of ataxia telangiectasia (AT), and from 4 control adult healthy persons. Caffeine (CF, 1 mM) was added at the beginning of the culture. In control cultures exposed to CF the frequency of CB was 1.9% and of CdB 1.3%. In cells of the AT homozygote, the frequency of CdB was 6.8% in the absence and 8.7% in the presence of caffeine, the frequencies of CB being 3.4 and 10.9%, respectively. In AT heterozygous cells treated with CF, CdB increased 13-fold as compared to a less than 3-fold increase in control cells. Comparing the frequencies of CF-induced chromosomal lesions in control and AT heterozygous cells, potentiation factors (Pf) for the effect of 1 AT gene on cell sensitivity to CF (Pf [AT]) were 3.5 for CB, 6.6 for CdB and 5.5 for CA. These data demonstrate that lymphocytes of AT heterozygotes are significantly more sensitive to caffeine treatment in vitro in terms of increased frequency of CdB than normal cells, which may be useful for the diagnosis of carriers of this defective gene.

[Benzo(a)pyrene metabolism in human fibroblasts--effect of 7,8-benzoflavone]. / Metabolizm benzo(a)pirenu w fibroblastach ludzkich--wplyw 7,8-benzoflawonu.

Benzo(a)pyrene (BP) metabolism was studied in cultured fibroblasts from healthy donor. Cells were cultured in Eagle medium supplemented with 10% fetal calf serum, 2 mM 1-glutamine, 100 U/ml penicillin and 100 micrograms/ml streptomycin. Cultures were grown at 37 degrees C to confluence in 45 cm2 culture flasks containing 15 ml medium and refed with fresh medium 24 h prior to treatment with BP. Cells were treated for 24 h with [G-3H]BP diluted with BP to give a final concentration 10 microM and a specific activity of 0.3 Ci/mmol. The metabolites were extracted by ethyl acetate, dried with Na2SO4, evaporated with nitrogen and injected into high pressure liquid chromatograph. The column (LiChrosorb RP 18) was eluted with a linear gradient of 60% methanol in water to 100% methanol in 45 min at a flow rate 0.8 ml/min. Radioactivity of fractions was measured. Following metabolites were identified: 3-hydroxy-BP (23.7%), 9-hydroxy-BP (17.0%), quinones (22.9%), 7,8-dihydroxy-BP (6.1%), 9,10-dihydroxy-BP and other derivatives (30.3%). 7,8-benzoflavone--an inhibitor of BP hydroxylase and epoxide hydrase, strongly inhibited the metabolism of BP in human fibroblasts, changing the proportions in the amounts of the metabolites. The ratio of phenols to the other metabolites increased twice under the influence of 7,8-benzoflavone. This suggests that 7,8-benzoflavone has the stronger inhibitory effect on epoxide and diol formation in comparison with BP hydroxylation.

The inhibitory effect of theophylline on cell cycle kinetics of human lymphocytes in vitro.

The effect of theophylline (TF) on proliferation of lymphocytes in phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) freshly stimulated 3-4 days cultures or of 14-days cultured lymphoblasts was studied. Proliferation was estimated by measurement of incorporation of tritiated thymidine (3H-TdR), and by microscopic analysis of cellular divisions progression up to the 4th generation of cells cultured in presence of 5-bromodeoxyuridine (BrdUrd). The strongest inhibition of proliferation was observed when TF was added at the beginning of the cultures. However, when TF was added for the last 20 h of the cultures, a significant decrease in number of the third (M3) and fourth (M4) generation cells was noted and M3/M4 ratio increased from 6.4 up to 19.1. TF inhibited also incorporation of 3H-TdR into cultured lymphoblasts. The obtained data indicate an inhibitory effect of TF both an activation and cell cycle progression of lymphocytes.