Unilateral areolar sebaceous hyperplasia in a male.
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Adult↗
Biomedical subjects
C De la Torre
Publications and source records attributed to C De la Torre.
Chronic leg ulcers and basal cell carcinoma.
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Aged↗
DNA injury induced by 5-aminouracil and caffeine in G2 checkpoints path of higher plant cells.
This work evaluated the qualitative and quantitative cellular changes induced by treatment with 5-aminouracil (5-AU) and a combination of 5-AU and caffeine in plant cells in relation to DNA damage, repaired damage, and residual damage. As biological material, Allium cepa L. root tips were used, grown in filtered water, in darkness, with aeration at constant temperature of 25 degrees C +/- 0.5. Cell populations were synchronized using 5 mM caffeine in order to study the effects of 5-AU and caffeine/5-AU combined treatment on the DNA content and their incidence in the entrance to mitosis. The results showed a delay in the G2 period due to induced DNA damage by the 5-AU and caffeine/5-AU combined treatment, shown by aberrant metaphases, anaphases and telophases. The effect of caffeine in the combined treatment was heightened in spite of lengthening the checkpoints route that retains the cells in G2. The existence of G2 checkpoints was shown in the cell population studied, inducing lesions in the DNA, chromosomic aberrations and cellular instability.
Caffeine↗
Nuclear ploidy is contingent on the microtubular cycle responsible for plant cytokinesis.
Division of the plant cell relies on the preprophase band of microtubules (PPB)-phragmoplast system. Cells of onion (Allium cepa L.) root meristems were rendered binucleate by preventing the consolidation of cell plate formation in telophase with 5 mM caffeine. These binucleates developed either a single PPB around one of their two nuclei or two PPBs, one per nucleus, in the prophase of the ensuing mitosis. Prophase cells developing one single PPB were shorter in length (42.3 +/- 4.1 microm) than those developing 2 PPBs (49.8 +/- 4.1 microm), and interphase duration was inversely related to cell length. Cells whose length was less than or equal to 42 microm, i.e., which had not even reached the mean size of the small binucleates in prophase, were followed throughout mitosis. In metaphase, they always assembled two mitotic spindles (one per nucleus). However, the cells that had assembled a single PPB also developed a single phragmoplast in telophase, leading to polyploidization. As these meristematic cells were not wide enough to accommodate the midzones of both mitotic spindles in any single plane transversal to the cell elongation axis, the spindles tilted until their midzones formed a continuum where the single common phragmoplast assembled. Its position was thereby uncoupled from that of the preceding PPB. Subsequently, the chromosomes from two different half-spindles were included, by a common nuclear envelope, in a single tetraploid nucleus. Finally, the cytokinetic plate segregated the two tetraploid nuclei formed at each side of the phragmoplast into two independent sister cells.
Cytokinesis↗
Systemic photosensitivity to quinapril.
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Aged↗
Z-DNA, a new in situ marker for transcription.
Z-DNA forms transiently behind the active RNA polymerases, because of the mechanical torsional stress produced during transcription. In this paper, we explore the possibility that the distribution of Z-DNA stretches signals the sites related to nuclear transcription. To localize transcription, the in situ assay for active RNA polymerases, that allows the elongation of the already initiated transcripts but no initiation of new ones (run-on experiments), was carried out in isolated nuclei of Allium cepa L. root meristems. Both nucleolar and non-nucleolar sites appeared labelled. Nucleoli were most active in transcription than the multiple non-nucleolar foci altogether. In situ immunodetection of Z-DNA provided images that were comparable to those obtained after the run-on assay, with one exception: while Z-DNA and transcription sites were scattered throughout the whole nucleus, Z-DNA also accumulated in the nuclear periphery, where no transcription foci were detected in run-on assays. The peripheral Z-conformation signals might correspond to dsRNA segments present in the pre-mRNA in the process of their export to cytoplasm. The Z-containing structures nearly disappeared when non-nucleolar RNA polymerase II-dependent transcription had been previously abolished by the adenosine analogue DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole). This inhibition selectively decreased the amount of all nucleoplasmic Z structures. On the other hand, the inhibition of the nucleolar RNA polymerase I by cordycepin (3'-deoxyadenosine) prevented the presence of Z-DNA in nucleoli. We propose to use the in situ immunodetection of Z-DNA as a marker of the transcription level in both nucleolus and non-peripheral nucleoplasmic regions of nuclei. Co-detection of Z-DNA and of intermediate filament (IF) proteins, the major components of the nuclear matrix, was also carried out. The IFA antibody recognizes a conserved epitope essential for dimerization of the multiple IF proteins. They co-localized with most nucleolar Z-DNA, but not with the nucleoplasmic ones. In the nuclear periphery, the Z-positive signals were adjacent to the IF proteins constituting the lamina, though both signals did not often co-localize.
Allium↗
G2 checkpoint targets late replicating DNA.
In the multinucleate cells induced in Allium cepa L. meristems, the nuclei surrounded by the largest cytoplasm environment complete replication earlier (advanced nuclei), but have a longer G2, than the others (delayed nuclei). Thus, all nuclei break down the nuclear envelope and start metaphase simultaneously. The present report shows that this synchronization relies on a checkpoint mechanism. When completion of replication was prevented in the delayed nuclei (due to in vivo 5-aminouracil feeding initiated when the advanced nuclei were already in G2), the metaphase was also further delayed in the advanced ones. In turn, some of the delayed nuclei overrode the G2 checkpoint (adaptation) and entered into mitosis with broken chromatids (Del Campo et al., 1997). Anoxic UVA (313 nm) irradiation apparently prevents the binding of regulatory proteins to Br-DNA. The present report shows that late replicating sequences are the targets of the checkpoint signal produced by the still replicating nuclei. This signal delays metaphase in the advanced nuclei, whose DNA is already fully replicated. Thus, when the already replicated sequences of late replicating DNA was modified in the advanced nuclei by bromosubstitution followed by anoxic UVA irradiation, they entered into mitosis without any delay, ignoring the inhibitory signals produced by the still replicating nuclei.
Animals↗
Human syndromes with genomic instability and multiprotein machines that repair DNA double-strand breaks.
The present report deals with the functional relationships among protein complexes which, when mutated, are responsible for four human syndromes displaying cancer proneness, and whose cells are deficient in DNA double-strand break (DSB) repair. In some of them, the cells are also unable to activate the proper checkpoint, while in the others an unduly override of the checkpoint-induced arrest occurs. As a consequence, all these patients display genome instability. In ataxia-telangiectasia, the mutated protein (ATM) is a kinase, which acts as a transducer of DNA damage signalling. The defective protein in the ataxia-telangiectasia-like disorder is a DNase (the Mre11 nuclease) that in vivo produces single-strand tails at both sides of DSBs. Mre11 is always present with the Rad50 ATPase in a protein machine: the nuclease complex. In mammals, this complex also contains nibrin, the protein mutated in the Nijmegen syndrome. Nibrin confers new abilities to the nuclease complex, and can also bind to BRCA1 (one of the two proteins mutated in familial breast cancer). BRCA1 has a central motif that binds with high affinity to cruciform DNA, a structure present in places where the DNA loops are anchored to the chromosomal axis or scaffold. The BRCA1 x cruciform DNA complex should be released to allow the nuclease complex to work in DNA recombinational repair of DSBs. BRCA1 also acts as a scaffold for the assembly of ATPases such as Rad51, responsible for the somatic homologous recombination. Loss of the BRCA1 gene prevents cell survival after exposure to cross-linkers. The BRCA1-RING domain is an E3-ubiquitin ligase. It can mono-ubiquitinate the FANCD2 protein, mutated in one of the Fanconi anemia complementation groups, to regulate it. Finally, during DNA replication, the nuclease complex and its activating ATM kinase are integrated in the BRCA1-associated surveillance complex (BASC) that contains, among others, enzymes required for mismatch excision repair. In short, the proteins missing in these syndromes have in common their BRCA1-mediated assembly into multimeric machines responsible for the surveillance of DNA replication, DSB recombinational repair, and the removal of DNA cross-links.
Apoptosis↗
Behaviour of ribosomal genes and nucleolar domains during activation in sugarcane (Saccharum officinarum L.) root primordia: from the unsoaked quiescent state to the steady state of proliferation.
Changes in the organisation of ribosomal genes and nucleolar protein components were analysed in sugarcane (Saccharum officinarum L. cv Cristalina) from the time the quiescent primordia of the radical bands of nodes were stimulated to proliferate by water imbibition, until the meristematic population reached the steady state of proliferation in the growing roots. The kinetics of proliferation was evaluated by flow cytometry, and by the mitotic indexes, in roots of different lengths. All the quiescent cells were in a pre-replicative state (G0), with a 2C DNA content. During their activation process, they progressively reached the steady state of proliferation (mitotic index 7%), with rather fixed frequencies for cells with 2C (G1), 4C (G2), and values between them corresponding to cells replicating their DNA. Decondensation of the ribosomal genes was followed by FISH with probes for the major 25S and 18S rRNAs, and variations in the numbers of nucleoli were recorded in squashed cells after silver staining. The ultrastructure of nucleoli was analysed by electron microscopy, using the EDTA regressive staining for ribonucleoproteins. Quiescent nucleoli showed a clear segregation of their main components: Fibrillar Centre, Dense Fibrillar Component and Cajal's bodies while lacked any Granular Component. However the proliferating ones showed them highly intermingled, except for the Cajal's bodies. Our results revealed a high plasticity of the nucleolar domains in response to cell activation, and allowed to establish a correlation between dispersion of NORs with formation of small fibrillar centers and a nucleolus with all its domains intermingled, and the activation of cell proliferation during root sprouting.
Cell Cycle↗
Replication and G2 checkpoints: their response to caffeine.
Under long hydroxyurea treatments, evidence was obtained for the sequential activation of four checkpoints located between the onset of S phase and mitosis in Allium cepa L. root meristems. Biparametric flow cytometry (Br-DNA/total DNA) showed that cells initially accumulated at early S phase but, after a delay, they resumed replication and paused again at mid S phase. Cells not only overrode this second replication block but also any G2 checkpoint they encountered. Thus, a late mitotic wave was produced in the presence of hydroxyurea. The wave was formed by cells that had apparently completed their replication (normal mitoses), while others displayed anaphases/telophases with less than the expected DNA content and with chromosomal breaks (aberrant mitoses). The presence of aberrant mitoses is direct evidence for the undue override of the two G2 checkpoints responsible for surveillance of completion of DNA synthesis and repair, respectively. Caffeine selectively abrogated the G2 block produced by the checkpoint that controls post-replication DNA repair, as it advanced the entry of cells into an aberrant mitosis. However, caffeine proved not to be the universal checkpoint-evading agent as postulated. Caffeine did not modify the spontaneous override of the replication checkpoints. Moreover, it seems to enforce the checkpoint that controls the completion of DNA synthesis, as the appearance of the late wave of normal mitoses produced in the presence of hydroxyurea was prevented by the use of caffeine.
Caffeine↗
Identification of Mycobacterium marinum in sea-urchin granulomas.
BACKGROUND: Sea-urchin granuloma is a chronic granulomatous reaction arising after injury with sea-urchin spines. Classified as an allergic foreign-body type of granuloma, it is believed to be a delayed-type reaction to an as yet unidentified antigen. In a clinicopathological study, 50 biopsy specimens from 35 patients diagnosed as having sea-urchin granuloma caused by Paracentrotus lividus, we found different inflammatory patterns that in some cases suggested a mycobacterial infection. OBJECTIVES: To investigate and identify mycobacterial DNA in formalin-fixed and paraffin-embedded skin biopsy specimens diagnosed as sea-urchin granulomas. METHODS: A search combining polymerase chain reaction amplification using Mycobacterium genus-specific primers, and subsequent restriction enzyme analysis enabling identification to the species level, was performed in 41 samples. RESULTS: Amplification of a 924-bp DNA fragment encoding mycobacterial 16S rRNA gene was positive in eight biopsy specimens from seven patients (21%). M. marinum-specific restriction patterns were identified in three samples. CONCLUSIONS: Although further controlled studies are necessary, from these data it would appear that mycobacteria may play a pathogenic role in some cases of sea-urchin granuloma.
Adolescent↗
Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity.
When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase. In this study, we analyzed chromosome structure in cells that bypassed this checkpoint. We observed a novel type of chromosome aberration, which we call omega-figures. These are entangled chromosome regions that indicate the persistence of catenations between nonhomologous sequences. The number of omega-figures per cell increased sharply as cells evaded the transient block imposed by the topo II-dependent checkpoint, and the presence of caffeine (a checkpoint-evading agent) potentiated this increase. Thus, the removal of nonreplicative catenations, a process that promotes chromosome individualization in G2, may be monitored by the topo II-dependent checkpoint in mammals.
Animals↗
Competence for assembly of sister chromatid cores is progressively acquired during S phase in mammalian cells.
Condensed sister chromatids possess a protein scaffold or axial core to which loops of chromatin are attached. The sister cores are believed to be dynamic frameworks that function in the organization and condensation of chromatids. Chromosome structural proteins are implicated in the establishment of sister chromatid cohesion and in the maintenance of epigenetic phenomena. Both processes of templating are tightly linked to DNA replication itself. It is a question whether the structural basis of sister chromatid cores is templated during S phase. As cells proceed through the cell cycle, chromatid cores undergo changes in their protein composition. Cytologically, cores are first visualized at the start of prometaphase. Still, core assembly can be induced in G1 and G2 when interphase cells are fused with mitotic cells. In this study, we asked if chromatid cores are similarly able to assemble in S-phase cells. We find that the ability to assemble cores is transiently lost during local replication, then regained in chromosome regions shortly after they have been replicated. We propose that core templating occurs coincident with DNA replication and that the competence for the assembly of the sister chromatid cores is acquired shortly after passage of replication forks.
Animals↗
Acrochordons are not a component of the Birt-Hogg-Dubé syndrome: does this syndrome exist? Case reports and review of the literature.
Multiple fibrofolliculomas, trichodiscomas, and acrochordons compose the triad of cutaneous lesions characterizing the Birt-Hogg-Dubé syndrome, inherited in an autosomal dominant fashion. We report a case of a family who had the triad of tumors of the Birt-Hogg-Dubé syndrome. Two members were observed clinically and histologically. Biopsies of the facial papules disclosed features of the fibrofolliculoma/trichodiscoma spectrum. Lesions that were clinically acrochordon-like proved to correspond to the same histopathologic spectrum. The characterization of the nature of the acrochordon-like lesions in our patients and the review of the literature allow us to question if acrochordons (skin tags) should be maintained as a component of this association. In light of our conclusion that fibrofolliculoma, trichodiscoma, and the acrochordon-like lesions are histologic variations of a single lesion, we further question whether the term "syndrome" is valid.
Female↗
Necrobiosis lipoidica: a case with prominent cholesterol clefting and transepithelial elimination.
Transepithelial elimination of degenerated collagen through the hair follicle in necrobiosis lipoidica is rare, clinically manifesting as comedo-like plugs. Also unusual in necrobiosis lipoidica is the finding of cholesterol cleft formation. We report a case of necrobiosis lipoidica with transepithelial elimination of cholesterol crystals through hair follicles. This has been described in necrobiotic xanthogranuloma, demonstrating some overlap in the histopathologic findings in both necrobiotic granulomas. Additional criteria should be used to establish the diagnosis.
Aged↗
Long-standing translucent tumor on the groin. Diagnosis: mucinous carcinoma of the skin.
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Adenocarcinoma, Mucinous↗
The positional control of mitosis and cytokinesis in higher-plant cells.
The present work establishes a correlation between cell length and patterns of mitotic microtubular assemblies in Allium cepa L. root meristems. Binucleate cells were formed by a short caffeine treatment which aborted the formation of the phragmoplast during telophase. The largest binucleate cells (about 50 microns in length) behaved as two contiguous mononucleate cells in their next mitosis: they developed two preprophase bands (PPBs), one around each nucleus, where two spindles and two phragmoplasts were subsequently formed. On the other hand, the shortest binucleate cells (about 36 microns in length) formed a single PPB at the site of the aborted phragmoplast and, in the medium-sized cells (about 44 microns) in which the single PPB formed around the nucleus possessing the largest cytoplasmic environment, the two mitotic spindles and the new phragmoplasts moved to, or were assembled in the position of the phragmoplast that had been aborted one cycle earlier. Some rules derive from these observations. First of all, the aborted phragmoplast left a signal for microtubule positioning which was still operative one cycle later, in two-thirds of the bimitoses. Also, that formation of the PPB is dispensable. Moreover, its development does not always predict the future division plane, because of the presence of competing old signals which are stronger than those shed by the PPB in the same mitosis, but which fade away with distance. Finally, the positional signals were reinforced when the ratio of monomeric to fibrillar actin was increased by cytochalasin D during their shedding. When this drug was given simultaneously with caffeine, the frequency of bimitoses which, one cycle later, developed spindles and phragmoplasts in the positions of the old phragmoplast increased. On the other hand, those frequencies dropped in relation to control when the cytochalasin D treatment took place during bimitosis, indicating that at this time the treatment reinforced the signals produced in bimitosis itself.
Allium↗
Replication of 5 S ribosomal genes precedes the appearance of early nuclear replication complexes.
The present work shows that replication of the 5 S ribosomal genes differs in time and 3'deoxyadenosine sensitivity from replication of other nuclear genes, in Allium cepa L. root meristems. Fluorescence in situ hybridization with the pTa794 DNA probe which contains a complete 410 bp 5 S gene from Triticum aestivum allowed to detect four clusters of 5 S genes in these diploid cells (2n = 16), two of them in the short arm of the smallest metacentric chromosomal pair 7. Replication of the 5 S ribosomal genes occurred very early in interphase, as discerned by their resolution as doubled spots only two hours after interphase was initiated in synchronous binucleate cells. Codetection of nuclear replication (by immunodetection of 5-bromo-2'-deoxyuridine incorporation) showed that the replication of the 5 S ribosomal genes occurred before any incorporation of 5-bromo-2'deoxyuridine could be detected in the nuclei. The earliest Br-DNA detected in these cells followed a radial pattern from different foci apparently dispersed along some chromosomal arms. These structures seem to represent early replication complexes, as a result of the displacement of multiple DNA forks from the foci known as pre-replication complexes where the replication machinery of the earliest replicating genes assembles. No consistent positional correlation existed between the formation of the early replication complexes and the already replicated 5 S ribosomal clusters. Finally, nuclear replication but not that of the 5 S genes was prevented by 3'deoxyadenosine, and the earliest replicating 5 S ribosomal gene cluster differed in both sister nuclei resulting from the segregation of one single chromosome in anaphase.
Cell Nucleus↗