1,721,094 research outputs found
Management of adrenal cysts.
No full textAdrenal cysts have been traditionally managed by excision to rule out malignancy. We reviewed the 613 cases of adrenal cysts (including 6 new cases of our own) to evaluate whether this is still appropriate. Descriptive statistics and distribution of each pathologic type have been updated, based on 515 cases, and have changed from statistics compiled on 155 cases by G. A. Absehouse et al. Only seven per cent of all adrenal cysts are malignant or potentially malignant. There is only one reported case of a malignancy found in a nonfunctioning adrenal cyst that was initially thought to be benign. In this case, no CT or aspiration was performed. There have been 19 cases of adrenal cysts managed with aspiration. All were nonfunctioning and benign. One had a bloody aspirate. Reaccumulation occurred in 32 per cent of the cases (six cases); six per cent were symptomatic, four per cent were excised. Follow up was available in 15 cases from 4 months to 3.5 years. Management of the patient with a suspected adrenal cyst should include a careful history and physical and biochemical screening to rule out a functioning lesion. A CT scan, and aspiration of the cyst with a cystogram should be performed to confirm a simple cyst of the adrenal. If the suspicion of malignancy is low, and the lesion is nonfunctional, the adrenal cyst may be managed by aspiration alone. If the cyst recurs and is asymptomatic, it may be observed. If a symptomatic cyst recurs, it may be reaspirated or excised
Commentary to: Mutations of the PI3KCA gene in ovarian and breast cancer
No full textObjective: to conduct a mutational analysis of the PIK3CA gene
in ovarian and breast tumors and correlate the
molecular results with histological types
Redistribution of DNA topoisomerase II β after in vitro stabilization of human erythroleukemic nuclei by heat or Cu++ revealed by confocal microscopy
No full textUsing confocal laser scanning microscope and a monoclonal antibody we have examined by means of indirect immunofluorescence techniques the distribution of DNA topoisomerase IIβ (the 180-kDa nucleolar isoform of topoisomerase II) following stabilization of isolated nuclei by exposure to moderate heat (37°or 42°C) or Cu++. In intact cells the antibody specifically decorated the nucleoli. The same pattern was maintained if nuclei were incubated at 0°C in a buffer containing spermine/spermidine/KC1 or stabilized by means of 0.5 mM Cu++ for 10 minutes at 0°C in the same buffer. On the contrary, if stabilization was performed by incubating the nuclei either at 37°or 42°C, the immunoreactivity dispersed all over the nucleus, forming numerous speckles. This phenomenon was not detected if, in addition to spermine/spermidine/KC1, the incubation buffer also contained 5 mM Mg++ and the temperature was 37°C. If the stabilization was performed at 42°C, Mg++ failed to maintain the original distribution of DNA topoisomerase IIβ, as seen in intact cells. The analysis on 2-D optical section showed the alteration of the nucleolar profile, particularly at 37°C, even when the samples were treated with Mg++. The 3-D reconstruction figured out the irregularity of the surface at 37°C and the variations of the volume occupied by the fluorescent figures. These were in close proximity to each other both in intact cells and in 0°C incubated nuclei; they showed a certain degree of shrinkage in 0°C plus Cu++ exposed samples (-20% of the volume), and, on the contrary, the labeled structures were scattered in a volume increased two- or threefold when exposed to 37°or 42°C, respectively. The addition of Mg++ restored the original spatial relationship and volume at 37°C, but not at 42°C, where the volumetric analysis showed an increase of about 50%. Our results demonstrate that heat stabilization of isolated nuclei in a buffer without Mg++ (i.e., a technique often employed to prepare the nuclear matrix or scaffold) cannot be considered an optimal procedure to maintain the original distribution of protein within the nucleus
Intranuclear translocation of phospholipase C β2 during HL-60 myeloid differentiation
No full textPhospholipases C (PLC) beta3, gamma1, and gamma2 were detected in nuclei of HL-60 promyelocitic leukaemia cells. When HL-60 cells undergo terminal myeloid differentiation in the presence of ATRA, the beta2 isoform appeared inside nuclei and was up-regulated until 72 hours of ATRA treatment. The beta3 isozyme was also increased until 72 hours and both isoforms lowered their intranuclear amount at 96 hours and following days of treatment. By contrast PLC gamma1 and gamma2 progressively increased in the nucleus during granulocytic differentiation even after 72 hours of treatment. Terminal differentiation was characterised by the expression of high levels of PLC gamma1 and gamma2 and by low levels of PLC beta2 and beta3 in the nucleus. PIP2 and PIP hydrolysis paralleled the prevalence of the beta or gamma subfamily, respectively. Moreover, at all the examined times no changes of PLCs in the whole cell were detectable, indicating a de novo nuclear translocation of the beta2 and an increased accumulation of beta3, gamma1, and gamma2 isoforms. Thus, the intranuclear presence, expression, and activity of PLC isozymes, which are modulated during differentiation of HL-60 cells, implicate a role for nuclear phosphoinositide signalling in the process of cell maturation. In particular the nuclear translocation of PLC beta2 candidates this PLC as a key enzyme in the granulocytic differentiative commitment of HL-60 cells
Protein kinase C isoforms and lipid second messengers: a critical nuclear partnership?
No full textA growing body of evidence, accumulated over the past 15 years, has highlighted that the protein kinase C family of isozymes is capable of translocating to the nucleus or is resident within the nucleus. The comprehension of protein kinase C isoform regulation within this organelle is under development. At present, it is emerging that lipid second messengers may play at least two roles in the control of nuclear protein kinase C: on one side they serve as chemical attractants, on the other they directly modulate the activity of specific isoforms. One of the best characterized lipid second messenger that could be involved in the regulation of nuclear PKC activity is DAG. The existence of two separate pools of nuclear DAG suggests that this lipid second messenger might be involved in distinct pathways that lead to different cell responses. Nuclear phosphatidylglycerol, D-3 phosphorylated inositol lipids and nuclear fatty acids are involved in a striking variety of critical biological functions which may act by specific PKC activation. The fine tuning of PKC regulation in cells subjected to proliferating or differentiating stimuli, might prove to be of great interest also for cancer therapy, given the fact that PKC-dependent signaling pathways are increasingly being seen as possible pharmacological target in some forms of neoplastic diseases. In this article, we review the current knowledge about lipid second messengers that are involved in regulating the translocation and/or the activity of different protein kinase C isoforms identified at the nuclear level
Prereplicative increase of nuclear matrix-bound DNA polymerase-alpha and primase activities in HeLa S3 cells following dilution of long-term cultures.
No full textWe investigated the association of DNA polymerase and DNA primase activity with the nuclear matrix in HeLa S3 cells diluted with fresh medium after having been cultured without any medium change for 7 days. Flow cytometric analysis demonstrated that just before dilution about 85\% of the cells were in the G1 phase of the cycle, whereas 8\% were in the S phase. After dilution with fresh medium, 18-22 h were required for the cell population to attain a stable distribution with respect to the cell cycle. At that time, about 38\% of the cells were in the S phase. DNA polymerase and DNA primase activity associated with the nuclear matrix prepared from cells just before dilution represented about 10\% of nuclear activity. As judged by [3H]-thymidine incorporation and flow cytometric analysis, an increase in the number of S-phase cells was evident at least 6 h after dilution. However, as early as 2 h after dilution into fresh medium, a striking prereplicative increase of the two activities was seen in the nuclear matrix fraction but not in cytosol or isolated nuclei. Both DNA polymerase and primase activities bound to the matrix were about 60\% of nuclear activity. Overall, the nuclear matrix was the cell fraction where the highest induction (about 10-fold) of both enzymatic activities was seen at 30 h after dilution, whereas in cytosol and isolated nuclei the increase was about two- and fourfold, respectively. Typical immunofluorescent patterns given by an antibody to 5-bromodeoxyuridine were seen after dilution. These findings, which are at variance with our own previous results obtained with cell cultures synchronized by either a double thymidine block or aphidicolin exposure, strengthen the contention that DNA replication is associated with an underlying nuclear structure and demonstrate the artifacts that may be generated by procedures commonly used to synchronize cell cultures
Lipid signaling and cell responses at the nuclear level
No full textThe nucleus is known to be a site for an active lipid metabolism. Although phospholipids are present in the nuclear envelope, evidence suggests that they are also located further inside the nucleus. The function of these intranuclear lipids has escaped clarification for many years. Early experiments showed that they can interact with DNA double helix affecting its thermal stability and can influence RNA synthesis in isolated nuclei. However, in the last 10 years several investigations have suggested that they may be involved in signal transduction pathways at the nuclear level and a growing body of evidence supports this hypothesis
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