Raman cooling of cesium below 3 nK: New approach inspired by Lévy flight statistics.
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Biomedical subjects
Publications and source records attributed to C Salomon.
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A randomized clinical trial was conducted to compare the results of automated percutaneous discectomy with those of chemonucleolysis in 141 patients with sciatica caused by a disk herniation; 69 underwent automated percutaneous discectomy and 72 were subjected to chemonucleolysis. The principle outcome was the overall assessment of the patient 6 months after treatment. Treatment was considered to be successful by 61% of the patients in the chemonucleolysis group compared with 44% in the automated percutaneous discectomy group. At 1-year follow-up, overall success rates were 66% in the chemonucleolysis group and 37% in the automated percutaneous group. Within 6 months of treatment, 7% of the patients in the chemonucleolysis group and 33% in the discectomy group underwent subsequent open surgery. The complication rates of both treatment groups were low, with the exception of a high rate of low-back pain in the chemonucleolysis group (42%). The results of this trial confirm previous controlled studies on chemonucleolysis and suggest that controlled studies should be carried out before automated percutaneous discectomy can be considered a useful intervention.
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To study alterations in cellular gene expression in mouse kidney cell cultures infected with simian virus 40 (SV40) or polyomavirus, we performed a differential screening of a mouse kidney cDNA library with probes prepared from mRNAs of virus-infected and mock-infected cells. We isolated and characterized cDNA recombinant pKT13 which detected increased mRNA levels in infected cells. Sequence analysis of pKT13 revealed close to 100% homology with the 3'-end of mouse fibronectin (FN) mRNA. Since primary cultures of baby mouse kidney cells have been extensively characterized in our laboratories, we studied FN gene expression at different stages of uninfected and virus-infected cultures. High levels of FN and of its mRNA were found in the kidneys of suckling mice, while in primary cultures of proliferating epithelial kidney cells the expression of FN was very low until the cultures became confluent. Thereafter FN increased and reached high levels in cells which were irreversibly arrested in phase Go and which had apparently exhausted their finite division potential. Infection of confluent cultures with polyomavirus or SV40 resulted in a further stimulation of FN gene expression. However, during abortive infection with SV40, FN mRNA and FN levels decreased with emergence of transformed cells and were low in an established SV40-transformed mouse kidney cell line. These changes in FN gene expression suggest that high levels of FN might be indicative in vivo for terminal differentiation and in vitro for cellular senescence.
SV40 and polyoma virus induce a mitotic host reaction in confluent, Go-arrested primary mouse kidney cell cultures. To define the primary effects of infection we constructed a cDNA library corresponding to polyA+ mRNA isolated shortly after onset of polyoma T-antigen synthesis. By differential screening of the library we have isolated and then sequenced cDNA recombinant 24p3; determined by Northern blotting, 24p3 mRNA steady state levels increased in parallel with polyoma and SV40 T-antigen synthesis. Since this rapid and early increase was particularly striking (14-20 fold) in SV40-infected cells, we studied the molecular mechanism of induction in this virus-cell system. We show that wt SV40 large T-antigen is required for the increase in 24p3 mRNA levels. The results tend to exclude that this increase is due to an SV40-induced stabilization of the 24p3 mRNA, or to an SV40-induced stimulation of transcription of the 24p3 gene; they are compatible with the working hypothesis that SV40 large T-antigen increases the efficiency of processing, possibly splicing, of the 24p3 pre-mRNA. The biological implications of these results are discussed.
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Five cases (four women and one man) with primary Gougerot-Sjögren syndromes presenting as interstitial pulmonary fibrosis are reported. The main point of interest was the severity of the pulmonary changes: effort dyspnoea from the outset, radiological interstitial pneumonitis, restrictive syndrome with a CO diffusing capacity less than 50 p. 100 of theoretical values in 4 cases. Broncho-alveolar lavage was performed in all patients: it showed a high polynuclear neutrophil and particularly high eosinophil counts. Lung biopsy showed severe fibrotic changes. The pulmonary changes dominated the clinical presentation in all patients and the Gougerot-Sjögren syndrome was only diagnosed after systematic examination completed by biopsy of the accessory salivary glands. In the absence of an associated connective tissue disease, these cases of the Gougerot-Sjögren syndrome were considered to be primary. Four patients were given steroid therapy but this did not prevent a fatal outcome in two cases after 6 and 14 months respectively. The clinical states of the other patients were unaffected by treatment. Twenty-one other, but less severe cases, have been previously reported. They confirm that interstitial pulmonary fibrosis observed during the Gougerot-Sjögren syndrome does not differ from idiopathic pulmonary fibrosis and that observed in other connective tissue diseases. Nevertheless, analysis of our cases showed that biopsy of the accessory salivary glands should be part of the routine investigation of apparently idiopathic pulmonary fibrosis. These pulmonary changes may be life-threatening when associated with a primary Gougerot-Sjögren syndrome.
Using three different polyomavirus hr-t mutants and two polyomavirus mlT mutants, we studied induction of S-phase by mutants and wild-type virus in quiescent mouse kidney cells, mouse 3T6 cells, and FR 3T3 cells. At different times after infection, we measured the proportion of T-antigen-positive cells, the incorporation of [3H]thymidine, the proportion of DNA-synthesizing cells, and the increase in total DNA, RNA, and protein content of the cultures. In permissive mouse cells, we also determined the amount of viral DNA and the proportion of viral capsid-producing cells. In polyomavirus hr-t mutant-infected cultures, onset of host DNA replication was delayed by several hours, and a smaller proportion of T-antigen-positive cells entered S-phase than in wild-type-infected cultures. Of the two polyomavirus mlT mutants studied, dl-23 behaved similarly to wild-type virus in many, but not all, parameters tested. The poorly replicating but well-transforming mutant dl-8 was able to induce S-phase, and (in permissive cells) progeny virus production, in only about one-third of the T-antigen-positive cells. From our experiments, we conclude that mutations affecting small and middle T-antigen cause a reduction in the proportion of cells responding to virus infection and a prolongation of the early phase, i.e., the period before cells enter S-phase. In hr-t mutant-infected mouse 3T6 cells, production of viral DNA was less than 10% of that in wild-type-infected cultures; low hr-t progeny production in 3T6 cells was therefore largely due to poor viral DNA replication.
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We studied synthesis of viral and cellular RNA in the presence and absence of 5-fluorodeoxyuridine (FdU, an inhibitor of DNA synthesis) during lytic infection with polyoma virus in confluent, primary mouse kidney cell cultures. In the presence of FdU, synthesis of early 19S polyoma mRNA and of polyoma tumor (T)-antigen, i.e. expression of the early viral gene, is rapidly followed by a mitogenic reaction of the host cell; it leads to an increase of 30 +/- 5% in cellular, mainly 28S and 18S rRNA, followed by activation of the cellular DNA-synthesizing apparatus. Polyoma-induced cellular RNA synthesis is paralleled by increased production of early 19S mRNA and begin of expression of the late viral genes, leading to synthesis of small amounts of late 19S and 16S mRNAs. Changed expression of the viral genome occurs in the absence of detectable synthesis of polyoma DNA I. Infection in the absence of FdU induces the same sequence of events; it is followed, however, by duplication of the mouse cell chromatin (S-phase) and production of progeny virus.
The polyoma mRNA's present in the cytoplasm of primary cultures of mouse kidney cells during lytic infection were characterized by sedimentation velocity analysis and by hybridization to polyoma DNA fragments generated by a specific endonuclease of Hemophilus parainfluenzae (Hpa II).
Heterogeneous polyoma giant RNA molecules have been isolated by oligo(dT)- cellulose chromatography during the late phase of a lytic cycle of infection of mouse kidney cell cultures. These RNAs have sedimentation coefficients in denaturing Me2SO gradients that are greater than 26S and thus apparently correspond to RNA molecules larger than one strand of polyoma DNA. Approximately 15% of total nuclear polyoma late giant RNAs contained tracts of poly(A) and were retained by oligo(dT)-cellulose. The polyoma late giant RNAs as well as heterogeneous nuclear RNAs (HnRNAs) were found to have a slightly lower sedimentation rate in Me2SO-chloral hydrate density gradients than sedimentation values in sucrose gradients indicated. Even when synthesis of viral DNA and the production of capsid protein are blocked by 5-fluorodeoxyuridine (FdU), 10% of polyoma-specific RNA (as determined by sedimentation analyses under aqueous conditions) was shown to contain tracts of poly(A). In contrast to our findings on polyoma late giant RNA, nuclear polyoma RNA synthesized in the presence of FdU sedimented in denaturing Me2SO-chloral hydrate gradients considerably slower (from 15 to 30S) in relation to HnRNA and ribosomal precursor RNA. The sedimentation pattern in denaturing Me2SO gradients suggest that Py RNA synthesized late in lytic infection in the presence of FdU may be no longer than one transcript of Py DNA.