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Biomedical subjects

J Rech

Publications and source records attributed to J Rech.

At least 19 recordsLinked to original sources
PubMed2006

[Superior vena cava syndrome: Catheter association as a rare cause].

HISTORY AND FINDINGS: A 78 year-old-woman was admitted with a swollen face, edema of the lower eyelids and dyspnea. The past medical history revealed an ovarian carcinoma treated with polychemotherapy. Half a year before the patient had been investigated for similar clinical symptoms but no underlying cause had been detected. The histology of an enlarged axillary lymph node did not show a malignancy. The symptoms persisted after angioedema-inducing drugs had been discontinued. INVESTIGATIONS: Initial CT scan, magnetic-resonance tomography as well as positron emission tomography failed to explain the clinical findings. Also, testing of serological, immunological and endocrinological tests as well as the differential blood count did not reveal a likely cause of the clinical symptoms. However, 4 weeks later, a repeat CT scan showed a stenosis of the superior vena cava (SVC) establishing the diagnosis of an SVC syndrome. TREATMENT AND COURSE: The port catheter tipp was localized horizontal to the vena cava superior and was touching the vein wall. Removal of the catheter and subsequent balloon dilatation of the stenosis immediately lead to a reduction of the eyelid swelling. CONCLUSIONS: Hence, in a case of an SVC-syndrome, complete stenosis caused by an implanted venous access system should be considered though it is rare.

Aged↗
PubMed2006

Plasmapheresis therapy in an elderly patient with rapidly progressive Henoch-Schönlein purpura with disseminated organ involvement.

Henoch-Schönlein purpura (HSP) frequently occurs in children below the age of 15 years and is rare with increasing age. Prognosis and therapy largely depend on the clinical presentation. The disease may be preceded by an upper respiratory tract infection, and drugs have also been implicated in the pathogenesis of the disease. Most children recover from the illness, whereas 40% of adults have persistent hematuria and 10% develop chronic renal failure. Recent studies strongly suggest that adults with HSP should be monitored for prolonged periods and treated aggressively. Here, we present a case of a patient with HSP who developed multiorgan failure requiring assistance in breathing and dialysis, and also sustained gastrointestinal bleeding despite aggressive immunosuppressive therapy. In analogy to published data in children with severe HSP, the patient was treated by plasma exchange in combination with low dose oral cyclophosphamide, while high dose steroids were reduced over time. The patient could be discharged 70 days after admission. One year after discharge, the patient is doing well without any signs of activity of HSP and completely unremarkable renal function. The maintenance daily dose of steroids is 7.5 mg.

Cyclophosphamide↗
PubMed2006

Schwinger boson approach to the fully screened Kondo model.

We apply the Schwinger boson scheme to the fully screened Kondo model and generalize the method to include antiferromagnetic interactions between ions. Our approach captures the Kondo crossover from local moment behavior to a Fermi liquid with a nontrivial Wilson ratio. When applied to the two-impurity model, the mean-field theory describes the "Varma-Jones" quantum phase transition between a valence bond state and a heavy Fermi liquid.

Journal Article↗
PubMed2006

Paraneoplastic syndrome, infection or arthritis: Difficulties in diagnosis.

Many different diseases have overlapping clinical symptoms. A major challenge in daily clinical practice is to differentiate between diseases associated with systemic inflammation, such as neoplasia, infection and autoimmune disease. We report on a 46-year-old Caucasian male with a 3-month history of rheumatoid arthritis presenting with dramatic weight loss and dysphagia. Computer tomography revealed multiple lesions in the liver and the spleen, strongly suggesting malignant disease of unknown origin. Surprisingly, on biopsy, the liver lesions drained pus. Workup revealed that the abscesses resulted from gastric perforation, which was the consequence of NSAR therapy for rheumatoid arthritis. Antibiotic therapy was initiated, abscesses diminished and dysfunctional deglutition improved. This unique case demonstrates in a dramatic way the difficulties in daily clinical practice to differentiate between paraneoplasia, infection and autoimmune disease and the potentially life-threatening consequences of their therapy.

Antirheumatic Agents↗
PubMed2002

Forced swimming evokes a biphasic response in CREB phosphorylation in extrahypothalamic limbic and neocortical brain structures in the rat.

The transcription factor cAMP response element-binding protein (CREB) plays a critical role in plasticity processes underlying learning and memory. We investigated the phosphorylation of CREB in rat brain after forced swimming, a stressor known to impact on higher limbic and neocortical brain areas. As shown by immunohistochemistry, forced swimming increased phosphorylated CREB (P-CREB) levels in the dentate gyrus, all neocortical areas, the medial, lateral and basolateral nuclei of the amygdala, cerebellum but not in the hypothalamic paraventricular nucleus. Distinct differences in the P-CREB pattern were observed in the deeper vs. superficial layers of the neocortex. The response in P-CREB was stressor type-specific because exposure to either ether or a cold environment was ineffective. The forced swimming-induced changes in P-CREB levels showed a biphasic time-course: an early peak detected at 15 min was followed by a marked drop at 60 min; a second rise starting after 1-2 h, reached maximal values between 6 and 8 h, and remained elevated for at least 48 h. Examination of the neuroanatomical induction pattern of the CRE-inducible immediate early gene product c-fos revealed that it was only partly overlapping with that of P-CREB. Western analyses showed that only the 43-kDa CREB protein (an enhancer of CRE-containing promotors) was phosphorylated after forced swimming, while other members of the CREB/ATF family (CREM, ATF-1 and ATF-2) remained unaffected. The NF-kappaB pathway was not activated, indicating that forced swimming does not unspecifically evoke transcription factor activation. Thus, in contrast to physical stressors, such as ether or cold exposure, forced swimming, a stressor with a strong psychological component, elicits the recruitment of the CREB pathway in a widespread manner in the limbic system and neocortex; brain regions known to be implicated in various forms of (stress-related) learning and memory.

Activating Transcription Factor 1↗
PubMed1999

Anchorage-dependent expression of cyclin A in primary cells requires a negative DNA regulatory element and a functional Rb.

Many cells, when cultured in suspension, fail to express cyclin A, a regulatory component of cell cycle kinases cdc2 and cdk2 and as a consequence, do not enter S phase. However, many cell type-specific differences are disclosed between not only normal and transformed cells, but also between cell lines whose proliferation is strictly anchorage-dependent. These apparent discrepancies are seen in established cell lines most probably because of adaptative events that have occurred during cell culture. We have therefore used primary cells to understand how cyclin A transcription is controlled by cell anchorage properties. To this aim, we have used embryonic fibroblasts from either wild type, Rb(-/-) or p107(-/-)/p130(-/-) mice and tested the effect of an ectopic expression of Rb mutants. In the experiments reported here, we show that anchorage-dependent expression of cyclin A (i) is reflected by the in vivo occupancy of a negative DNA regulatory element previously shown to be instrumental in the down regulation of cyclin A transcription in quiescent cells (Cell Cycle Responsive Element: CCRE) (ii) requires a functional Rb but neither p107 nor p130 (iii) mutation of the CCRE abolishes both adhesion-dependent regulation and response to Rb.

Animals↗
PubMed1998

[Cyclin A: a good markers for the study of cell cycle control and tumor progression?].

Cyclin A is a positive regulatory component of kinases required for the progression through S phase and for the transition between the G2 and M phases of the cell division cycle. Previous studies conducted in established cell lines and in primary human T lymphocytes, have demonstrated that the promoter of its gene is under negative transcriptional control in quiescent cells. The DNA sequences mediating this repression have been delineated through in vitro mutagenesis as well as in vivo genomic footprinting experiments. Indirect observations suggest the involvement of proteins related to the retinoblastoma tumor suppressor protein (pRb). Using primary fibroblasts from either pRb(-/-), p107(-/-), p130(-/-) or p107(-/-)/p130(-/-) mice, we show in this work that mutation of the pRb gene has the more profound effect on cyclin A transcription. Finally, normal fibroblasts cultured in suspension fail to express cyclin A and can no longer enter S phase and proliferate, revealing thus a dependence of cyclin A expression on cell anchorage. Our work suggests the existence of at least two sets of regulators controlling cell cycle progression. On the one hand, proteins like cyclin D1, whose expression is a direct consequence of the activation of the ras signalling pathway and on the other hand, proteins like cyclin A which are secondary response effectors. As a result, growth factor stimulation leads to a transcriptional activation of the former set, while the transcription of the latter set is under the control of a repressor whose effect is alleviated after triggering the ras cascade. The status of pRb thus dictates whether cells continue their progression through the cell cycle when ras is mutated, probably by allowing the uncontrolled expression of critical genes like cyclin A.

Animals↗
PubMed1997

Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules.

Cyclin A transcription is cell cycle regulated and induced by cell proliferative signals. To understand the mechanisms underlined in this regulation in normal human cells, we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes. Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells. Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective. In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites, the presence of at least three protein binding sites, two of which were constitutively occupied. They bind in vitro respectively ATF-1 and NF-Y proteins. The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone. The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation. Consistent with theses results, nuclear extracts prepared from quiescent cells formed a specific complex with this element, whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state.

Activating Transcription Factor 1↗
PubMed1996

Cyclin A expression is under negative transcriptional control during the cell cycle.

Transcription of the gene coding for cyclin A, a protein required for S-phase transit, is cell cycle regulated and is restricted to proliferating cells. To further explore transcriptional regulation linked to cell division cycle control, a genomic clone containing 5' flanking sequences of the murine cyclin A gene was isolated. When it was fused to a luciferase reporter gene, it was shown to function as a proliferation-regulated promoter in NIH 3T3 cells. Transcription of the mouse cyclin A gene is negatively regulated by arrest of cell proliferation. A mutation of a GC-rich sequence conserved between mice and humans is sufficient to relieve transcriptional repression, resulting in a promoter with constitutively high activity. In agreement with this result, in vivo footprinting reveals a protection of the cell cycle-responsive element in G0/early G1 cells which is not observed at later stages of the cell cycle. Moreover, the footprint is present in dimethyl sulfoxide-induced differentiating and not in proliferating Friend erythroleukemia cells. Conversely, two other sites, which in vitro bind ATF-1 and NF-Y, respectively, are constitutively occupied throughout cell cycle progression.

3T3 Cells↗
PubMed1994

Nuclear import of serum response factor (SRF) requires a short amino-terminal nuclear localization sequence and is independent of the casein kinase II phosphorylation site.

Serum stimulation of resting cells is mediated at least in part at the transcriptional level by the activation of numerous genes among which c-fos constitutes a model. Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory protein p62TCF/Elk-1. Both proteins are the targets of multiple phosphorylation events and their role is still unknown in the amino terminus of SRF. While the transcriptional activation domain has been mapped between amino acids 339 and 508, the DNA-binding and the dimerization domains have been mapped to between amino acids 133-235 and 168-235, respectively, no role has been proposed for the amino-terminal portion of the molecule. We demonstrate in the present work that amino acids 95 to 100 contain a stretch of basic amino acids that are sufficient to target a reporter protein to the nucleus. Moreover, this sequence appears to be the only nuclear localization signal operating in SRF. Finally, whereas the global structure around this putative nuclear location signal is reminiscent of what is found in the SV40 T antigen, the casein kinase II phosphorylation site does not determine the rate of cyto-nuclear protein transport of this protein.

Amino Acid Sequence↗
PubMed1989

Requirements for c-fos mRNA down regulation in growth stimulated murine cells.

The fos proto-oncogene is rapidly and transiently expressed in resting cells exposed to growth stimulation. This gene is down-regulated at least at two levels: transcriptional repression and mRNA degradation. To determine the sequences and the structures involved in mRNA instability, we analyzed in mouse Ltk- cells various fos/beta-globin constructs for their transcriptional activity and the half-lives of the corresponding RNAs. In these cells, rabbit beta-globin genes under the control of a 500 bp fos SRE (serum responsive element)/promoter region are transiently transcribed within 30 min after stimulation. Analysis of the decay kinetics of RNA originating from these constructs led to the following conclusions with respect to the nature of c-fos destabilizer elements: (i) 100 bases from c-fos 3' untranslated region are able to confer instability when inserted into a normally stable beta-globin RNA; (ii) however, the degradation is more rapid when the complete untranslated region is inserted; (iii) rapid mRNA breakdown requires more determinants than two AUUUA motives and is associated with a reduction in size, presumably due to a poly(A) shortening; (iv) remarkably, c-fos destabilizing sequences remain active even when part of the coding sequence.

Animals↗
PubMed1988

Role of RNA structures in c-myc and c-fos gene regulations.

Proto-oncogenes c-myc and c-fos are subjected to a complex set of controls operating both at the transcriptional and post-transcriptional levels. We report here that: (i) antisense transcription occurs at the murine c-myc locus. However, its biological significance remains to be established; (ii) transcription of both genes is regulated in various situations by a block to elongation of nascent RNA chains. In the case of c-myc, the blockade involves a RNA structure whose nature remains unknown; (iii) elements responsible for the high degree of instability of c-myc and c-fos mRNAs reside in their 3' non-coding regions. A U-rich region, reminiscent of that present in the granulocyte-monocyte colony-stimulating factor mRNA destabilizer, is likely to be involved in the rapid degradation of c-fos mRNA; (iv) exon 1 substitution by intron 1-derived sequences lessens or negates the effect of the 3' destabilizer in abnormal c-myc RNAs from Burkitt's lymphomas and mouse plasmacytomas.

Animals↗
PubMed1988

The regulatory strategies of c-myc and c-fos proto-oncogenes share some common mechanisms.

There is evidence for both transcriptional and post-transcriptional levels of regulation of c-fos and c-myc proto-oncogenes. Transcription of both genes can be regulated at the level of initiation. However, it was recently shown in various situations for c-myc, and in one case for c-fos, that these genes can also be down-regulated by a block to elongation of nascent RNA chains. Both c-myc and c-fos mRNAs are known to be extremely unstable (half-lives around 10-15 min) and c-myc RNA turnover has been shown to be modulated under various physiological situations. Atypical c-myc RNAs found in certain mouse plasma cell tumors (MPCs) and Burkitt, lymphomas (BLs) are significantly and sometimes dramatically more stable than their normal counterparts. In this review we report that: i) transcriptional control elements reside in murine c-myc and c-fos first exons. Daudi cells provide an example of c-myc activation via removal of this block to elongation; ii) elements necessary for the rapid degradation of c-fos and c-myc RNAs reside in their 3' non-coding regions; iii) these destabilizing elements can be counteracted by atypical 5' sequences found in abnormal c-myc transcripts from BLs and mouse plasmocytomas.

Animals↗
PubMed1987

Regulation of c-fos gene expression in hamster fibroblasts: initiation and elongation of transcription and mRNA degradation.

Rapid and transient activation of both c-fos transcription and mRNA accumulation occurs when resting CCL39 hamster fibroblasts are serum-stimulated to grow. By using several combinations of serum and cycloheximide, a protein synthesis inhibitor, we showed that: i) addition of cycloheximide to resting cell elicits an increase in c-fos gene transcription located within the first 540 bases of the unit, suggesting that an "attenuation-like" mechanism, similar to that observed for c-myc, might be essential for c-fos transcriptional regulation; ii) it also prevents both transcriptional shutoff and mRNA degradation in serum-stimulated cells; iii) upon removal of cycloheximide, mRNA degradation resumes rapidly; deletion of a 130 bases long segment in the 3 non-coding region leads to a stabilization of c-fos mRNA lending experimental support to a putative destabilizer element within this sequence.

Animals↗