Biomedical subjects

C Berger

Publications and source records attributed to C Berger.

At least 109 records · Page 6Linked to original sources

PubMed1998

Diffusion-controlled DNA recognition by an unfolded, monomeric bZIP transcription factor.

Basic leucine zipper (bZIP) transcription factors are dimers that recognize mainly palindromic DNA sites. It has been assumed that bZIP factors have to form a dimer in order to bind to their target DNA. We find that DNA binding of both monomeric and dimeric bZIP transcription factor GCN4 is diffusion-limited and that, therefore, the rate of dimerization of the bZIP domain does not affect the rate of DNA recognition and GCN4 need not dimerize in order to bind to its specific DNA site. The results have implications for the mechanism by which bZIP transcription factors find their target sites for transcriptional regulation.

Amino Acid Sequence↗

PubMed1998

Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana.

The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Arabidopsis↗

PubMed1998

Phase II study of cisplatinum and carboplatinum (CACIS) combination in advanced stage neuroblastomas.

BACKGROUND: Platinum derivatives are, among others (cyclophosphamide, etoposide, doxorubicin), the most active drugs in neuroblastomas. As the combination of carboplatin (CBDCA) with cisplatinum (CDDP) was proven effective in some carcinomas, we proposed it as a second-line therapy in neuroblastoma. PROCEDURE: Nineteen children with neuroblastoma and primary refractory disease (seven cases) or relapse either untreated (eight cases) or resistant to second-line therapy (four cases), were treated with cisplatinum and carboplatinum (CACIS) combination. All but one patient had previously received CDDP (median 400: 200 to 1,200 mg/m2) and 15 out of 19 had also received CBDCA (median 1,600:800 to 5,000 mg/m2). Twelve had previously received intensification with megatherapy. The CACIS regimen included CBDCA (100 mg/m2/day as a 1-hour infusion, for 4 days) and simultaneous CDDP (25 mg/m2/day as a 3-hour infusion, for 4 days). RESULTS: Eight out of 19 patients (42%) achieved a partial response with a duration of response of 3 to 12 months (median 6). No patient achieved a complete response. The toxicity was mainly hematological, though one patient died after two courses of an interstitial pneumonia of unknown origin. Only one patient developed alopecia. The renal toxicity was low. CONCLUSIONS: The CACIS regimen is an effective combination of platinum derivatives. It may be proposed as second line protocol, especially for children with neuroblastoma who relapse after megatherapy.

Adolescent↗

PubMed1998

Identification of the sensory/motor area and pathologic regions using ECoG coherence.

An electrophysiologic mapping technique which enables identification of the central sulcus and pathologic cortical regions is described. Electrocorticographic recordings of 1 min duration were recorded from 25 patients who were undergoing resection of tumors in the sensory-motor region or being evaluated for temporal lobectomy for epilepsy. Analysis of the patterns of subdural inter-electrode coherence revealed low coherence across the central sulcus for 11/12 cases where its location could be verified with direct cortical stimulation and/or somatosensory evoked potential mapping. Regions of high coherence identified the location of tumors in the sensory-motor region for 10/10 cases. Over the temporal lobe, localized areas of high coherence were evident in 8/9 epilepsy patients, but were not indicative of the location of mesial temporal lobe tumors or inter-ictal spiking, when present. We conclude that analysis of cortical coherence patterns may be helpful for revealing the location of pathologic processes relative to critical cortical areas.

Adolescent↗

PubMed1998

Choroid plexus carcinomas in childhood: clinical features and prognostic factors.

OBJECTIVE: Choroid plexus carcinomas are rare tumors with dismal prognosis. The role of surgery has been well established, but the benefit of either chemotherapy or radiotherapy remains controversial. To determine prognostic factors and effects of different therapeutic modalities on the outcome, we have reviewed the French experience of choroid plexus carcinoma. METHODS: Twenty-two children were registered in the Société Française d'Oncologie Pédiatrique between 1984 and 1995. All these children underwent surgical resection of the primary tumor. The intent of postoperative treatment was to delay or to avoid radiation therapy. Nineteen children received postoperative treatment, with chemotherapy in 17 and radiation therapy in 2. Two responding patients underwent high-dose chemotherapy with stem cell rescue. RESULTS: The 5-year survival rate was 26%. The sole relevant prognostic factor was the extent of surgery. Patients with total or gross total resection had a 86% survival rate. Survival did not correlate with age, sex, delay between first appearance of symptoms and diagnosis, location of the primary tumor, tumor volume, or response to postoperative treatment. All but one patient with incomplete surgery had tumor recurrence within 2 to 23 months. CONCLUSION: Choroid plexus carcinoma has a very poor prognosis when surgery is incomplete. Aggressive surgical resection of the tumor is necessary for survival. Although chemotherapy gives promising responses, local control remains the main challenge, and "second look" surgery has to be considered for patients with incomplete resection.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Does NO regulate the cerebral blood flow response in hypoxia?

OBJECTIVES: To study whether nitric oxide (NO) affects the CBF response to hypoxic and carbon monoxide (CO) hypoxia. MATERIAL AND METHODS: We incrementally reduced arterial oxygen content in rats, by decreasing the concentration of inspired oxygen (20 rats) or by repeated CO inhalation (20 rats), and measured local CBF using the hydrogen clearance method. Ten animals of each group received 80 mg/kg NO synthase (NOS) inhibitor N-monomethyl-L-arginine intravenously prior to hypoxia, while 10 rats served as controls. RESULTS: Inhibition of NOS decreased mean CBF by 30% and increased cerebrovascular resistance by 70%. Under hypoxic hypoxia, mean oxygen reactivity of CBF (relative change of CBF to a change of arterial oxygen content) was 7.8%/vol% in control animals and 3.3%/vol% after NOS inhibition (P < 0.02). Under CO hypoxia, mean oxygen reactivity was 7.3%/vol% in control animals and 5.1%/vol% after NOS inhibition (P < 0.05). Inhibition of NOS diminished significantly the cerebral vasodilatory response during hypoxic hypoxia (P < 0.05) but only to a lesser extent during CO hypoxia. CONCLUSION: These observations suggest that NO is involved in cerebral oxygen vasoreactivity, particularly in severe hypoxia.

Animals↗

PubMed1998

Molecular analysis of critical sequences within the EBNA-2 type 1 gene from Epstein-Barr virus isolates from patients with infectious mononucleosis, tonsillar hyperplasia, and HIV infection.

EBNA-2 is the first protein to be detected after infection of primary B lymphocytes by Epstein-Barr virus (EBV) and plays an essential role as transcriptional activator in EBV-induced lymphocyte transformation. We analysed by PCR and sequencing regions of the EBNA-2 type 1 gene from isolates from 13 children with infectious mononucleosis (IM), 6 children with tonsillar hyperplasia (TH), and 9 patients with HIV infection followed longitudinally. We found in all three groups of patients frequent non-silent point mutations at positions 48990, 48991, 49021, 49057, 49083, 49089, 49091, 49113, 49119, 49140, 49156, and a triplet insertion at position 49136. While 4 out of 13 samples from patients with IM showed a mosaic pattern suggesting co-existence of more than 1 substrain of EBNA-2 type 1, none of the samples from TH showed this pattern consistent with substrain selection during clinical latency. No sequence changes were noted over time in samples derived from patients with HIV infection. We conclude that in analogy to the coexistence of several subtypes of EBNA-1 in healthy EBV carriers, samples from IM can harbor more than one subtype of the EBNA-2 type 1 gene.

Child↗

PubMed1998

[Treatment of infiltrating cancer of the bladder with cisplatin, fluorouracil, and concurrent radiotherapy: results of a pilot study].

PURPOSE: Pilot study to assess treatment feasibility and results of a 2-drug chemotherapy (CT) regimen administered concurrently with radiotherapy (RT) for muscle-invasive bladder cancer. MATERIALS AND METHODS: Fourty-six patients were included into a prospective study from December 1992 to April 1996. The median age was 66 years. Thirty-seven percent of the patients had T3B-T4 tumors, and 46% had benefited from prior macroscopically complete transurethral resection (TUR). Pelvic irradiation consisted of 50.4 Gy in 28 fractions over 39 days. Concurrent CT consisting of cisplatin (80 mg/m2/d1) and 5-fluorouracil (800 mg/m2/d2 to 5) by continuous infusions (5-FU) was delivered during the first and fifth weeks of radiation therapy. Twenty-three patients received two additional courses of adjuvant CT with cisplatin, methotrexate and vinblastin (MCV). RESULTS: The median follow-up was 38 months. The feasibility of concurrent CT-RT was excellent: 96% of the patients completed radiotherapy and 100% of them received the two courses of P-FU. The acute toxicity was mild: no hematological toxicity or renal toxicity over grade II, 4 cases of bowel or rectal reversible grade III toxicity and 2 cases of reversible grade III cystitis. A complete response was achieved in 30 out of the 42 evaluable patients (65.2%). Nine patients received an immediate salvage treatment (3 TUR, 3 additional radiotherapy and 3 cystectomies). Ten patients had local failure. Projected 3-year locoregional control was 49% for the 46 patients. Projected overall 3-year survival was 53%. Functional results were good for disease-free patients with preserved bladder: 1 grade I, 3 grade II, and no grade III cystitis. CONCLUSION: Concurrent 2-drug chemoradiotherapy with cisplatin and 5-fluorouracil is feasible without major toxicity and offers a potentially curative and conservative treatment for patients with localized muscle-invasive bladder cancer.

Aged↗

PubMed1998

[Surgical management of malignant bone tumors in the child. Saint-Etienne Hospital experience, apropos of 17 cases].

From 1980 to 1997, seventeen children were treated for malignant bone tumors in the Department of Paediatric Surgery of the Saint-Etienne Hospital, with an average follow-up of 6 years and 3 months (2M-17Y). The histologic diagnoses were osteosarcomas (12 cases) and Ewing's sarcomas (5 cases). All children were treated surgically. For the 12 lower limb tumors, the techniques used were prosthetic replacement in 7 cases (associated with bone allograft in 3 cases), amputation in 3 cases and isolated bone allograft in 2 cases. The two ilium tumors were treated by resection and reconstruction with autologous bone graft. A single resection was performed for the shoulder-blade Ewing's tumors and a prosthesis for the 2 proximal humerus tumors. Six children died during follow-up. The authors stress that carcinologic resection is a priority before functional results. They insist on the mechanical failures of implants and on the difficulties of reoperations.

Adolescent↗

PubMed1998

[Interest of gene amplification by PCR for the diagnosis of Mycoplasma pneumoniae infections in the child].

Between december 1996 and february 1998, rhinopharyngeal and tracheal aspirates from 165 children exhibiting symptoms compatible with M. pneumoniae infection were tested by a PCR method using in the same tube primers specific for M. pneumoniae P1 adhesin gene and for a human control gene. The positive cases were controlled using culture and/or serology. PCR was positive in 22 out of 165 samples (13.3%); an evaluation of the clinical and biological data was possible in 20 of these infected children. From 17 PCR positive respiratory samples tested by culture, 13 (76.5%) grew M. pneumoniae. From 14 serum specimens tested by ELISA, 12 exhibited specific IgM (3 of them with low titers); cold agglutinins were detected in all 7 tested sera. Only one case was not confirmed by any of the 3 former markers. The mean age of patients was 8.1 years. The main clinical symptoms included fever > 38 degrees C, cough, clinical and radiological pneumonia in 90, 95, 50 and 85% of cases, respectively. Neurological symptoms were the main clinical manifestation in 3 patients; another child exhibited a pneumonia associated to an hemophagocytic syndrome and a bone marrow failure which needed a graft. These results emphasize the value of PCR for the rapid diagnosis of M. pneumoniae infection in children.

Adhesins, Bacterial↗

PubMed1997

Selective outgrowth of a posttransplant B-immunoblastic lymphoma expressing a latent membrane protein-1 deletion variant.

BACKGROUND: Posttransplant lymphoproliferative disorders are generally associated with Epstein-Barr virus (EBV) and are of B cell origin. We report the case of a B-immunoblastic lymphoma that developed in a pretransplantation EBV-seronegative woman 4 months after kidney transplant from her HLA-haploidentical brother. The patient successfully underwent immunotoxin therapy for lymphoma and has been in remission for 36 months. METHODS: Latent EBV genomes were identified by polymerase chain reaction, and the purified amplification products were directly sequenced with [35S]dATP. RESULTS: Molecular analysis of the latent membrane protein (LMP)1 oncogene of EBV, which was expressed in most tumor cells, revealed a 30-base pair deletion. No wild-type LMP1 sequences were found. Analysis of peripheral blood mononuclear cells from the EBV-seropositive donor showed the presence of both the LMP1 deletion variant and the wild-type sequence. The LMP1 deletion variant and the wild-type sequence were also identified within peripheral blood mononuclear cells of the EBV-seroconverted kidney recipient 20 months after lymphoma therapy. CONCLUSION: This pattern is consistent with a natural growth advantage of B cells expressing the LMP1 deletion variant in the immunocompromised host.

Adult↗

PubMed1997

Termination of mammalian rDNA replication: polar arrest of replication fork movement by transcription termination factor TTF-I.

A replication fork barrier (RFB) at the 3' end of eukaryotic ribosomal RNA genes blocks bidirectional fork progression and limits DNA replication to the same direction as transcription. We have reproduced the RFB in vitro in HeLa cell extracts using 3' terminal murine rDNA fused to an SV40 origin-based vector. The RFB is polar and modularly organized, requiring both the Sal box transcription terminator and specific flanking sequences. Mutations within the terminator element, depletion of the RNA polymerase I-specific transcription termination factor TTF-I, or deletion of the termination domain of TTF-I abolishes RFB activity. Thus, the same factor that blocks elongating RNA polymerase I prevents head-on collision between the DNA replication apparatus and the transcription machinery.

3T3 Cells↗

PubMed1997

Natural 30 base pair and 69 base pair deletion variants of the LMP1 oncogene do stimulate NF-kappaB-mediated transcription.

An increasing number of reports shows a link between the Epstein-Barr virus (EBV) and lymphoid neoplasia. The latent membrane protein 1 (LMP1) is likely to play a determinant role in this process since this EBV encoded protein has oncogenic properties and is usually expressed in EBV-associated lymphoproliferative diseases (LPD), except Burkitt's lymphoma. We previously identified in LPD patients mutational hot spots and a 30 bp or 69 bp deletion in the LMP1 gene region coding for the C-terminal domain. These deletions are located in an area shown to be important for the activation of the transcription factor NF-kappaB. These findings lead us to test whether these natural deletion variants may have a functional effect. We measured the stimulation of their activity using a luciferase reporter plasmid containing NF-kappaB responsive elements. We tested the NF-kappaB inducing activity of four naturally occurring LMP1 deletion variants. Our results show that these deletion variants activate NF-kappaB to the same level as the wild-type form, indicating that the crucial residues for NF-kappaB activation are conserved among the variants isolated and lie within the last 32 amino acids of the C-terminal domain of the LMP1 oncogene.

Base Composition↗

PubMed1997

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Adenocarcinoma↗

PubMed1997

Epstein-Barr virus-associated persistent polyclonal B-cell lymphocytosis with a distinct 69-base pair deletion in the LMP1 oncogene.

Epstein-Barr virus (EBV) genomes have been detected in peripheral blood lymphocytes (PBL) of patients with persistent polyclonal B-cell lymphocytosis (PPBL). This is consistent with the hypothesis that latent EBV infection is involved in the pathogenesis of this disorder. Two EBV-encoded proteins expressed in viral latency are the latent membrane proteins 1 and 2A (LMP1 and LMP2A). We have studied the LMP1 oncogene and the LMP2A gene in a female patient with PPBL and her five siblings. A cell line derived from peripheral blood lymphocytes (PBL) of the patient was also analyzed. A distinct 69-base pair deletion was identified within the carboxy terminal NF-kappa B activation domain of the LMP1 oncogene in PBL of the patient and in the cell line, whereas none of the siblings harbored this deletion. The tyrosine-signaling motif and the HLA A2.1 epitope of the LMP2A gene were wild type in the patient and all siblings. The presence of a 69-base pair deletion variant of the LMP1 oncogene within the lymphocytes of a PPBL patient but absence of this deletion variant in the unaffected siblings suggests a direct implication of altered LMP1 oncoprotein-dependent function in the pathogenesis of PPBL.

Amino Acid Sequence↗

PubMed1997

[Comparison of subjective and objective parameters after oculomotor muscle surgery].

BACKGROUND: In regard to quality-control studies concerning strabismus surgery we were interested in a comparison of subjective and objective parameters after squint surgery. MATERIALS AND METHODS: In a questionnaire 175 patients were asked for their evaluation of the functional and cosmetic results 1 week and 6 weeks after squint surgery. Parallel, objective parameters like reduction of the squint angle and quality of stereopsis were documented. RESULTS: Overall 94.2% of patients with esotropia (n = 52) were satisfied cosmetically and 5.8% were not 1 week after squint surgery was performed. In the group of a patients with exotropia (n = 36), 91.7% of the patients were satisfied cosmetically and 8.3% were not. Even in cases of esotropia or exotropia no changes in the quality of stereopsis were noted by some patients or they could not be mentioned in the questionnaire. Some patients did not appreciate the improvement of binocular function found in our examination. CONCLUSIONS: Good congruence between objective and subjective results 1 week after squint surgery was found.

Adolescent↗

PubMed1997

Temporal order of replication of mouse ribosomal RNA genes during the cell cycle.

The timing of replication of mouse ribosomal RNA (rRNA) genes was determined in cultured cells by using 5-bromodeoxyuridine labeling of DNA coupled with synchronization. Two subclasses of rRNA genes were characterized that differ in their temporal order of replication during S-phase. Approximately half of the rDNA repeat units replicated primarily during the first half of S-phase and the other 50% preferentially in the second half. This difference in replication timing was consistently observed for the approximately 400 rDNA repeat units of NIH3T3 fibroblasts, but not for plasmid DNA containing fragments of rRNA genes that had been stably transfected into the genome of these cells. The rDNA fragments inserted into these transfection vectors contained the recently mapped origin of bidirectional replication with or without amplification-promoting sequences, or none of the above. Since the plasmid DNA that was integrated into the host cell genome replicated randomly during S-phase we conclude that the integrated plasmid DNA is either replicated from a chromosomal origin in the neighborhood of its integration site or that inserts are replicated from their own origins and the timing of replication is determined by flanking sequences.

3T3 Cells↗

PubMed1997

Use of a DNA typing method to investigate a fatal perinatal infection due to Staphylococcus aureus.

The aim of this study was to determine, by random amplified polymorphic DNA analysis, the origin of a fatal Staphylococcus aureus perinatal infection which occurred after multiple cervical examinations before induction of labor for patient convenience. This DNA typing method was able to demonstrate that this infection originated from S. aureus genital carriage and urinary tract infection of the mother, and was not acquired in the hospital. This observation argues for the systematic screening of genital flora for highly virulent strains before induction of labor for non medical reasons. In addition, the DNA typing method used demonstrates that one neonate was subsequently infected by the strain responsible for the chorioamnionitis. This shows that molecular typing methods can help determine hospital staff responsibility.

Adult↗