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Biomedical subjects

S Gangloff

Publications and source records attributed to S Gangloff.

At least 19 recordsLinked to original sources
PubMed2001

Mycobacterium avium infection in CD14-deficient mice fails to substantiate a significant role for CD14 in antimycobacterial protection or granulomatous inflammation.

CD14 is a pattern-recognition receptor implicated in the inflammatory response to microbial components such as lipopolysaccharide, peptidoglycan and lipoarabinomannan. In this work, we made use of CD14-deficient (CD14-/-) mice to evaluate the relative importance of CD14 in response to infection with viable, intact cells of Mycobacterium avium in vitro and in vivo. Following co-incubation of either bone marrow-derived macrophages (Mphi) or thioglycollate-elicited peritoneal Mphi from CD14-/- mice with viable M. avium, tumour necrosis factor (TNF) production was significantly reduced and delayed compared to TNF secretion by infected CD14+/+ Mphi. However, following intravenous infection with a M. avium strain of either high virulence (TMC724) or intermediate virulence (SE01), there was no difference in the bacterial loads of lungs, livers or spleens at 3, 5 and 8 weeks postinfection in CD14-/- mice when compared with syngeneic CD14+/+ mice. At these time-points, TNF and interferon-gamma (IFN-gamma) mRNA expression in the liver was similar in infected CD14+/+ and CD14-/- mice, and granuloma formation and expression of inducible nitric oxide synthase within granuloma Mphi was the same in both mouse groups. In conclusion, although the absence of CD14 results in significantly reduced and delayed TNF production in response to stimulation with M. avium in vitro, there is no evidence that CD14 plays a significant role in either the antibacterial defence or the chronic granulomatous reaction to M. avium infection in vivo.

Animals↗
PubMed2000

Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases.

DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination and repair. In the yeast Saccharomyces cerevisiae, the absence of the Sgs1 helicase results in genomic instability and accelerated ageing. In human cells, mutations in orthologues of SGS1 lead to Bloom (BS), Werner (WS) or Rothmund-Thomson (RTS) syndromes, which are rare, autosomal recessive diseases characterized by genetic instability associated with cancer predisposition. Although data concerning these human diseases are accumulating, there is still no clear idea of the function of the proteins involved. Here we show that sgs1Delta mutants are deficient in DNA repair and are defective for induced recombination events that involve homologous chromosomes. The role of homologous recombination is further evidenced in haploid cells in which both Sgs1p and Srs2p are absent. Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity. Our data suggest that some defects observed in BS, WS or RTS are the consequence of unrestrained recombination.

Bloom Syndrome↗
PubMed1999

The essential role of yeast topoisomerase III in meiosis depends on recombination.

Yeast cells mutant for TOP3, the gene encoding the evolutionary conserved type I-5' topoisomerase, display a wide range of phenotypes including altered cell cycle, hyper-recombination, abnormal gene expression, poor mating, chromosome instability and absence of sporulation. In this report, an analysis of the role of TOP3 in the meiotic process indicates that top3Delta mutants enter meiosis and complete the initial steps of recombination. However, reductional division does not occur. Deletion of the SPO11 gene, which prevents recombination between homologous chromosomes in meiosis I division, allows top3Delta mutants to form viable spores, indicating that Top3 is required to complete recombination successfully. A topoisomerase activity is involved in this process, since expression of bacterial TopA in yeast top3Delta mutants permits sporulation. The meiotic block is also partially suppressed by a deletion of SGS1, a gene encoding a helicase that interacts with Top3. We propose an essential role for Top3 in the processing of molecules generated during meiotic recombination.

Amino Acid Sequence↗
PubMed1997

[Spontaneous elimination by the natural tracts of screws of anterior cervical osteosynthesis. Apropos of a case].

PURPOSE OF THE STUDY: The authors report a case of a wellknown but very unusual complication of cervical spine anterior osteosynthesis: spontaneous recurrent elimination of anterior fixation device through the gastrointestinal track, with good outcome. MATERIALS AND METHODS: The patient (75 years old) was operated on for cervical myelopathia due to cervical stenosis. Surgical treatment included an anterior release with corporectomy of C4, C5 and C6 and iliac graft insertion, and fixation using plate and screws. Immediate post-operative course was uneventful. Plate incurvation and rupture were observed during the second post-operative month, with partial anterior migration of the lower screw. As the patient complained of dysphagia, removal of osteosynthesis was decided and scheduled 3 days later; however the screw was missing on a pre-operative radiograph. It was found on a routine abdominal X-Ray, and it passed out during the following week. Dysphagia disappeared in a few days and removal of osteosynthesis was given up for fear of oesophageal complications. Further evolution was favourable. Cervical fusion was obtained uneventfully. Post-operative myelmogram showed a good canal enlargement. The patient was temporarily lost for follow-up and was asked for review 2 years later. Mild difficulty in swallowing saliva was still present without dysphagia. On routine cervical X-Rays another screw had disappeared again. Oesophagoscopy was proposed but not accepted by the patient because he felt not significantly disturbed. DISCUSSION AND CONCLUSION: Complications associated with oesophageal perforation may range from massive infection and death to spontaneous resolution. Erosion due to extruded bulky constructs leads to persistent fistula with abscess or septic diffusion. Perforation due to complete migration of small foreign bodies like screws gives possibility of spontaneous oesophageal closure and healing without significant morbidity. The spontaneous recurrent elimination of 2 screws gives to this observation a very outstanding feature.

Aged↗
PubMed1996

Extraperitoneal approach to the lumbar spine with video assistance.

STUDY DESIGN: Description of a new operative techniques for anterior lumbar and lumbosacral fusion using an anterior approach optimized by video assistance. OBJECTIVES: To propose a less invasive technique for anterior lumbar fusion with low-grade morbidity. SUMMARY OF BACKGROUND DATA: Either anterior transperitoneal or anterolateral extraperitoneal approaches commonly are performed, but each involves specific drawbacks. The authors attempted to modify and simplify these approaches with the addition of retroperitonoscopy. METHODS: A small, vertical 4- to 5-cm inclusion is made on the midline, centered on the umbilicus for the L4-L5 approach and halfway between umbilicus and public symphysis for the L5-S1 approach. The peritoneum is dissected from the left abdominal wall, and the anterior aspect of the spine progressively is exposed. The endoscope is introduced laterally, providing excellent visualization of the prevertebral area. A specially designed retractor allows retraction of the iliac vessels. RESULTS: A midline anterior approach allows disc resection and grafting in a strict midline position. The extraperitoneal approach simplifies the postoperative course. Video assistance permits an approach to the spine by a short incision and facilitates the prevertebral dissection. Surgery with video assistance should be differentiated from true endoscopic surgery, which is performed under CO2 insufflation with exclusive endoscopic vision. CONCLUSIONS: Video assistance allows for an anterior extraperitoneal approach in the lumbar spine and has the potential for lower morbidity, increasing the possibilities of anterior fusion in the management of lumber disc disease.

Adolescent↗
PubMed1996

[Prospects in video-assisted spinal surgery].

Advances in spinal surgery for both posterior procedures on herniated discs and anterior procedures involving the vertebral body have been greatly affected by developments in video-assisted techniques. Many of the procedures mentioned here are still in the development stage, others have proven their efficacy. Discoscopy, achieved by introducing the endoscope via a posterolateral route into the intervertebral disc, can be used for diagnosis and treatment of the disc and the end plates. Other techniques exploring the spinal canal are also being developed. With miniaturization, these techniques will undoubtedly be predominant in the near future. The anterior route is facilitated at the thoracic level by the pleural cavity. Current indications for anterior endoscopic spinal surgery are limited to cord compression syndromes, but perspectives for trauma or tumor surgery as well as reconstruction surgery for malformations in children are quite promising. On the lumbar level, surgery involving the lombo-sacral disc is the main indication for transperitoneal endoscopy. The risks (sepsis, occlusion, gas emboli) cannot be overlooked, but few complications have been observed to date. The retroperitoneal route can be used to approach the anterolateral aspect of the spine, particularly useful for the upper lumbar bodies. A third possibility is the extraperitoneal anterior route for video-assisted procedures from L2-L3 to L5-S1. Although video-assisted procedures have not yet been shown to improve long-term outcome after spinal surgery, the immediate post-operative period is greatly simplified, a point which may be of particular importance depending on the patient's general status.

Endoscopy↗
PubMed1996

Gene conversion plays the major role in controlling the stability of large tandem repeats in yeast.

The genomic stability of the rDNA tandem array in yeast is tightly controlled to allow sequence homogenization and at the same time prevent deleterious rearrangements. In our study, we show that gene conversion, and not unequal sister chromatid exchange, is the predominant recombination mechanism regulating the expansion and contraction of the rDNA array. Furthermore, we found that RAD52, which is essential for gene conversion, is required for marker duplication stimulated in the absence of the two yeast type I topoisomerases. Our results have implications for the mechanisms regulating genomic stability of repetitive sequence families found in all eukaryotes.

Base Sequence↗
PubMed1996

Results of surgical treatment of spinal thoracic and lumbar metastases.

The results of surgical treatment of vertebral metastases were evaluated from a retrospective review of a consecutive series of 100 patients, with special reference to anatomoclinical aspects and functional outcome. The primary tumour in most cases was lung, breast, or prostate; it was unknown in 11 cases. Diagnosis of the metastasis occurred 4-86 months after that of the primary tumour (lung metastasis: 4 months; breast metastasis: 86 months; prostatic metastasis: 22 months). Patients complained of vertebral pain in 96 cases and/or radicular pain in 43 cases. Intractable pain was observed in lung metastasis in particular. All patients received analgesics, and 57 received morphinics. Walking was impossible for 50 patients. Thirty-eight patients presented with neurologic deficit; neurologic status varied according to the primary tumour. Treatment included anterior surgery in 58 patients, posterior surgery in 33 patients, and combined surgery in 9 patients. Mean duration of hospitalisation was 12 days. No patient was admitted to the intensive care unit. Mean follow-up was 13.5 months. Eighty-nine patients were dead at follow-up, with an average survival of 10 months. Mean survival time was 7 months for patients with lung metastasis, 12 months for those with breast metastasis and 24 months for those with prostatic metastasis. Ten patients were still alive at follow-up (mean follow-up period 45 months, range 17-72 months). Analgesics were stopped for 62 patients following discharge from hospital. Morphinics had to be continued in seven patients. Thirty-five patients out of 50 (70%) recovered walking capacity. Neurologic status improved in 30 out of 38 patients. Although duration of survival was limited, surgery proved to be beneficial in providing a significant and early improvement in the functional status of more than 80% of patients. A precise evaluation of preoperative pain is necessary. Pain is dependent upon the bony lesion, the primary tumour, and the tumoral topography, which defines the surgical approach.

Analgesics↗
PubMed1996

Posttraumatic scoliosis.

A case of posttraumatic scoliosis due a misdiagnosed lumbosacral unilateral dislocation was observed 6 weeks after a traffic injury in a 15-year-old boy. Cobb angle was 30 degrees on T10-L4 with 20 degrees rotation on L1 and L2. Initial radiographs were normal. The scoliosis was corrected after surgical correction of the dislocation; at 5-year follow-up, the patient worked normally; there was no scoliosis. The suggested physiopathology of this structural scoliosis is similar to spondylolisthetic scoliosis of childhood in which asymmetrical forward displacement of the vertebral body results in rotational shift of the vertebra, with lumbar scoliosis. Correction of the scoliosis depends on correction of the lumbosacral dislocation.

Adolescent↗
PubMed1995

Recombinant BCG strains expressing the SIVmac251nef gene induce proliferative and CTL responses against nef synthetic peptides in mice.

CTL responses are known to be important for the control of HIV and SIV infections. Such responses are targeted against various components of these viruses including regulatory proteins like Nef. The SIVmac251nef gene was cloned in Mycobacterium bovis BCG under the control of P(AN), a promoter from Mycobacterium paratuberculosis. Nef was expressed as a fused polypeptide with ORF2, an open reading frame adjacent to P(AN). Mice inoculated with rBCG(SIVmac251nef) exhibited proliferative and CD8+ cytotoxic T-cell (CTL) responses against several Nef synthetic peptides. A mapping of the epitopes recognized by CTLs revealed that the central region of Nef is mainly involved in responses. This region had already been demonstrated to induce CTLs in experimentally SIV-infected macaques as well as in HIV-infected individuals. These results demonstrate the feasibility of constructing BCG vaccine strains expressing nef for eliciting cytotoxic responses.

Animals↗
PubMed1995

[Video-assisted anterior extra-peritoneal approach of the inferior lumbar spine].

PURPOSE OF THE STUDY: The aim of this study is to describe a new operative technique for anterior lumbar and lumbosacral fusion using a video assisted anterior extra peritoneal approach. MATERIAL: Ten patients were operated on. There were 3 men and 7 females. Age at operation ranged from 18 to 55. There were 8 degenerative and 2 iatrogenic discopathias. Fused level was L4-L5 (5 patients) and L5-S1 (5 patients). Average hospital stay was 6 days. METHODS: A small vertical 4-5 cm incision is made on the mid line, centered on the umbilicus for the approach to L4-L5, and between the umbilicus and pubis for the L5-S1 approach. The peritoneum is cleaved from the abdominal wall on the left side, and the anterior aspect of the spine is progressively freed. The endoscope is laterally introduced. It gives an excellent view of the prevertebral area. A specially designed retractor is used for retraction of the iliac vessels. Following removal of the intervertebral disc, a special spreader allows obtention of a normal intervertebral space height and insertion of an autogenous iliac graft. DISCUSSION: Anterior approach of the lumber intervertebral discs allows disc resection and grafting in a strict middle position. The extra peritoneal simplifies the postoperative course and avoids digestive and septic complications of the transperitoneal approach. The video assistance gives excellent exposure by a small incision with direct visual control; it should be differentiated form the true endoscopic lumbar surgery which is performed under C02 insufflation, with exclusive endoscopic vision and with instruments introduced through trocards. CONCLUSION: Video-assistance allows an approach to the lumbar and lumbosacral spine by an anterior non invasive extra peritoneal approach, with low morbidity, increasing the possibilities of anterior fusion in the treatment of lumbar discopathias and instability without radicular compromise.

Abdomen↗
PubMed1995

[Surgical treatment of cervical disk displacement. Anterior or posterior approach?].

PURPOSE OF THE STUDY: This study is a retrospective analysis of the treatment of cervical soft disc herniation comparing anterior and posterior approach. MATERIAL AND METHODS: Twenty eight patients presenting with cervico-brachial radiculopathy secondary to acute soft posterolateral disc herniation were reviewed. Cases with myelopathy or radiculopathy secondary to chronic spondylosis were excluded. Involved level was C5-C6 or C6-C7 in most cases. There were 14 females and 14 males. Age at operation averaged 44 years. Fourteen patients underwent an anterior approach with discectomy and fusion using autologous iliac bone graft. Average age was 46 years in this group with an average follow-up of 30 months. Average duration of surgery was 2 hours. Average hospital stay was 6 days. Fourteen patients underwent a posterior approach with partial lateral laminotomy extending medially for several millimeters over the facet joint. Extruded disc material was removed in 10 cases. No curettage was performed. Average age at surgery was 41 years with an average follow-up of 36 months in this group. Average duration of surgery was 70 minutes. Average hospital stay was 6 days. RESULTS: Patients were evaluated 3 months post-operatively and at their maximum follow-up. At 3 months follow-up, no patient complained of radicular pain; occasional cervical pain was present in 5 cases following posterior surgery but was not observed at late follow-up. Return to work was possible on an average of 3 months in both series. Results were graded as excellent, good, fair and poor. At late follow-up, in patients with a posterior approach, there were 8 excellent results, 5 good results with neck fatigue at work, and 1 fair result requiring analgesics. In patients with an anterior approach, there were 7 excellent results, 6 good results, and 1 fair result. Two patients complained of pain at the iliac donor site. DISCUSSION: These results suggest that the anterior approach gives better short term results, but no significant difference is observed between anterior and posterior approaches a few years after surgery. Although the anterior approach is more appropriate than the posterior one for the treatment of central disc herniation, the posterior approach may be considered as an alternative to anterior discectomy and fusion for antero-lateral soft disc herniation.

Adult↗
PubMed1994

Transcription, topoisomerases and recombination.

Transcription, DNA topoisomerases and genetic recombination are interrelated for several structural reasons. Transcription can affect DNA topology, resulting in effects on recombination. It can also affect the chromatin structure in which the DNA resides. Topoisomerases can affect DNA and/or chromatin structure influencing the recombination potential at a given site. Here we briefly review the extent to which homologous direct repeat recombination and site-specific recombination in eukaryotes are affected by transcription and topoisomerases. In some cases, transcription or the absence of topoisomerases have little or no effect on recombination. In others, they are important components in the recombinational process. The common denominator of any effects of transcription and topoisomerases on recombination is their shared role in altering DNA topology.

Animals↗
PubMed1994

Immunogenicity of polysaccharides conjugated to peptides containing T- and B-cell epitopes.

To develop a general model of polysaccharide-peptide vaccine, we have investigated the efficiency of linear peptides derived from protein SR, and adhesin of the I/II protein antigen family of oral streptococci, to act as carriers for two T cell-independent polysaccharides: serogroup f polysaccharide from Streptococcus mutans OMZ 175 (poly f) and Saccharomyces cerevisiae mannan. Peptide 3 (YEKEPTPPTRTPDQ) and peptide 6 (TPEDPTDPTDPQDPSS), accessible on the native SR protein as demonstrated by their reactivity in enzyme-linked immunosorbent assays with rat antisera raised against protein SR, correspond to immunodominant regions of SR. Peptide 3 contains at least one B- and one T-cell epitope, as demonstrated by its ability to induce peptide- and SR-specific antibody responses without any carrier and to stimulate the proliferation of rat lymph node cells primed either with free peptide or native SR, whereas peptide 6 contains only B-cell epitope(s). Peptide 3 was then covalently coupled though reductive amination to either poly f or mannan, and peptide 6 was coupled to poly f. Subcutaneous immunizations of rats with poly f-peptide 3 or mannan-peptide 3 conjugates produced a systemic immunoglobulin M (IgM) and IgG antibody response, and the elicited antibodies reacted with free poly f or mannan, peptide 3, protein SR, and S. mutans or S. cerevisiae whole cells. Rats immunized with poly f-peptide 6 did not develop any antipeptide or anti-SR response. Furthermore, a booster immunization of animals with poly f-peptide 3 or mannan-peptide 3 conjugates induced high titers of anti-peptide 3, anti-poly f, and antimannan antibodies, which occurred quickly. The response is anamnestic for the peptide and the polysaccharides and is characterized by an Ig switch from IgM to IgG. The data presented here confirm that the presence of B- and T-cell epitopes is necessary to induce an anamnestic antipeptide response and that a peptide containing relevant B- and T-cell epitopes can act as a good carrier in improving an antipolysaccharide anamnestic immune response.

Amino Acid Sequence↗