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M Favre

Publications and source records attributed to M Favre.

At least 19 recordsLinked to original sources
PubMed1996

Variability and phylogeny of the L1 capsid protein gene of human papillomavirus type 5: contribution of clusters of nonsynonymous mutations and of a 30-nucleotide duplication.

We analyzed the variability and established the phylogeny of the L1 capsid protein gene of 33 isolates of human papillomavirus type 5 (HPV5) obtained from epidermodysplasia verruciformis patients from different continents. By comparing the sequences of a 419-bp fragment with those published for two Japanese isolates, we found 12.9% variable nucleotide positions, defining 25 variants with mutation rates ranging from 0.2 to 8.8%. Such a high intratypic diversity is unusual among HPVs. Nine of the 139 encoded amino acids were variable and 12 protein variants were identified. Fifteen of the 16 substitutions observed were clustered in two short regions. A 9-amino-acid insert, already reported for the Japanese HPV5b isolate, was found within one of the regions in five isolates. Our data support that the insert arose from the duplication of a 30-nucleotide sequence. Phylogenetic trees distributed the DNA variants into three subtypes (a to c) with a divergence higher than 4.5% and allowed the recognition of European and African lineages. By contrast with the trees based on the HPV5 E6 gene, HPV5a DNA variants and the HPV5b variants lacking the insert constituted a single group in the L1 amino acid tree, probably reflecting different levels of structural constraints for the HPV5 L1 and E6 proteins. In that respect, the short variable L1 sequences should represent less constrained regions.

Amino Acid Sequence↗
PubMed1996

Decreased frequency of HLA-DRB1 13 alleles in Frenchwomen with HPV-positive carcinoma of the cervix.

Specific types of human papillomaviruses (HPV) are associated with most cases of pre-invasive and invasive neoplasia of the uterine cervix. HLA phenotype influences susceptibility and resistance to viral infections and may therefore influence the course of HPV-associated tumors. Some data suggest that specific HLA class-II alleles may be associated with protection from or susceptibility to papillomavirus-associated lesions, but these results are still controversial. Using molecular probes, we looked for associations between specific DQA1, DQB1, DRB1 HLA class-II alleles, HPV types and cervical cancer. The analysis was performed on a population of 126 patients with invasive cervical cancer. For HLA typing, 165 healthy individuals were taken as controls. The DRB1 1301/02 allele frequency significantly decreased in patients (11%) as compared to controls (29%). This difference in frequency was dependent on the HPV-positive status of tumors and was no longer significant in the group of HPV-negative lesions. The same trends were observed with the DRB1 1301/02-DQA1 0103-DQB1 0603 haplotype frequency. An increase in the frequency of the DRB1 1401/07 and DRB1 03 alleles was observed in patients under 40. Contrary to what has been reported in the literature, no increase in the DRB1 15 allele frequency was observed in our series and only a slight increase in the DQB1 03 frequency was found in patients (70%) compared to controls (58%). In our study, no positive correlations between cervical cancer in Frenchwomen and specific HLA DR-DQ haplotypes has been found. In contrast, a negative correlation between DRB1 1301/ 02 alleles and HPV-positive tumors has been observed. This may suggest a protective effect of DR13 against HPV-associated lesions of the cervix.

Adult↗
PubMed1995

A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors.

The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors.

Cell Line↗
PubMed1993

CD2 + CD19 + acute lymphoblastic leukaemia in 16 children and adults: clinical and biological features. Groupe d'Etude Immunologique des Leucémies (G.E.I.L.).

A small population of CD2 + CD19 + lymphoid cells have been suggested to be common lymphoid progenitors. CD2 + CD19 + biphenotypic ALL account for less than 2% of ALL. We analysed the clinical and laboratory features of a series of 16 patients with CD2 + CD19 + ALL. The incidence of tumoural syndrome was comparable to a previously published series of pre B-ALL but significantly different from that of T-ALL. The mean age of the 11 children of this series was 101 +/- 46 months, and differed significantly from that of children with pre B-ALL (P < 0.01). Complete remission was obtained for all patients except two adults. Only three relapses have been observed. Regardless of the presence of CD2 +, the 16 ALL could be classified as pre B-ALL, according to the nomenclature used by the GEIL. Nine samples could be analysed by Southern blotting. Seven had rearranged IGH genes, usually on both chromosomes. IGK rearrangement was observed in three cases. Only one case had rearranged both TCRG and TCR beta. The patterns observed here and those reported previously follow that of the pre B-ALL which confirms the engagement of most CD2 + CD19 + biphenotypic ALL in the B-lineage.

Adult↗
PubMed1993

Childhood condyloma acuminatum: association with genital and cutaneous human papillomaviruses.

We studied 25 children, age 7 months to 12 years 6 months, with anogenital warts, and their parents. In most children the warts were localized in the anal area, in 3 of 18 girls perianally and on the vulva, and in 4 girls exclusively on the vulva. Southern blot hybridization studies disclosed an association of condylomata with human papillomaviruses (HPV) 6 and 11 in 74% and HPV 2 in 17.4% of patients. The clinical features were similar in warts induced by genital and cutaneous HPVs. Even the HPV 2-associated warts in the vulva of two girls were typical of condyloma acuminatum. In all children with HPV 2-induced condylomata, cutaneous common warts coexisted, also induced by HPV 2. However, three mothers had cutaneous warts, and the children's condylomata were associated with HPV 6. Thus, the mere presence of skin warts in family members does not rule out other sources of infection. Sexual abuse was suspected in four girls and two boys, but was not confirmed in any. Nonsexual transmission could occur by persons with the lesions taking care of children. Perinatal transmission also appears to be an important route of infection in small babies. Infection in utero was probable in one girl in whom anal warts appeared in the first week of life and whose mother had cervical condylomata during pregnancy. This study provides further confirmation of possible nonsexual transmission of genital HPVs and the not infrequent association of childhood condylomata with HPV 2.

Anus Neoplasms↗
PubMed1993

Sporadic cases of Heck disease in two Polish girls: association with human papillomavirus type 13.

Two sporadic cases of Heck disease in Polish girls were associated with human papillomavirus 13. No other children and nobody from their surroundings had similar lesions. The course of the disease was chronic in both patients. The lesions regressed spontaneously in one girl within several years after some of the papules were excised. The second girl's warts persist after eight years.

Child↗
PubMed1993

Genetic heterogeneity of oncogenic human papillomavirus type 5 (HPV5) and phylogeny of HPV5 variants associated with epidermodysplasia verruciformis.

Variants of oncogenic human papillomavirus type 5 (HPV5), specifically associated with epidermodysplasia verruciformis, were recognized on the basis of the genetic heterogeneity of the E6 open reading frame (ORF). To further evaluate the genetic heterogeneity of HPV5, we sequenced the long control region (LCR), the E7 ORF, and the terminal parts of the E2 ORF of five previously characterized HPV5 variants and compared the data with the published HPV5a1 and HPV5b sequences. Alignment of the variants showed 140 (7.6%) variable nucleotides of 1,854 sequenced. Nucleotide substitution rates varied from 3.6% in the E7 ORF to 11% in the E6 ORF. By sequencing the variable region encompassing the LCR 3' part and the E6 ORF of isolates from six additional epidermodysplasia verruciformis patients, we identified three new variants and three already known variants, indicating the stability of HPV5 variants. This stability was further demonstrated by the identity of isolates obtained years later from benign and malignant lesions of three patients. Phylogenetic analysis of the 10 HPV5 variants distributed them into three groups, tentatively defining subtypes a, b, and c. The phylogenetic grouping shows no geographical dependence, a fact that may be related to the host restriction that characterizes HPV5 infections. No differences in the enhancer potential of the LCR or in the transactivating properties of the E2 protein assayed in vitro were observed among HPV5 variants. Whether HPV5 variants possess distinct biological properties in vivo remains to be determined.

Base Sequence↗
PubMed1993

[Human papillomavirus and nasosinusal inverted papilloma].

Eight inverted papillomas were evaluated for the presence of human papillomavirus (HPV) DNA. The techniques used were Southern Blot Hybridization in five cases and Polymerase Chain Reaction (PCR) in three cases. All eight lesions contained the characteristic features of inverted papillomas. Two lesions showed areas of dysplastic change and one lesion contained koilocytes. In three patients, invasive squamous cell carcinomas were found. The presence of HPV was noted in one of these specimen of inverted papilloma with squamous cell carcinoma. Specific testing for HPV types 6, 11, 16, 18 and 33 on this specimen was negative, thus indicating that the specimen is associated with a different HPV type. The results of this study, with only one case of positive HPV testing, leads us to question the precise role of HPV as an etiological agent in nasal inverted papillomas. The fact that this single positive case did not test positive for the HPV type 16 suggest that this is not the only "high risk" HPV type associated with the progression of inverted papilloma to a carcinoma.

Adult↗
PubMed1993

Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d'Etude Immunologique des Leucémies.

A group of 30 acute lymphoblastic leukemias (ALL) with the early pro-T phenotype CD7+/cCD3+/CD1-/CD3-/CD4-/CD8-were identified among 103 newly diagnosed ALL with T-lineage markers (T-ALL). Pro T-ALL was more often observed in adults, and showed a lower incidence of hyperleukocytosis than more mature T-ALL. Mediastinal masses and polar acid phosphatase positivity in blast cells were however observed with the same frequency in pro T-ALL and late T-ALL, and rearrangements of both T-cell receptor (TCR) beta and gamma genes were observed in half the pro T-ALL cases tested. The expression of CD34, DR, and myeloid (My) markers was significantly more frequent in pro T-ALL than in late T-ALL, and these three features were strongly linked. TCR gene rearrangements were two to three times more frequent in CD34- and My-pro T-ALL. However, both CD34+ and My+ pro T-ALL showed an incidence of mediastinal masses and polar acid phosphatase positivity similar to this observed in CD34- and My- cases. This supports the assumption that both types of ALL indeed are engaged in the T-lineage, and confirms intracytoplasmic cCD3 as the earliest marker for this lineage. Moreover, CD34 appears to persist up to an early stage of T-cell maturation, where the cells retain myeloid potentiality. Loss of CD34 correlates with TCR-beta gene rearrangement and definitive commitment to the T lineage. Event-free survival analysis suggested a poorer outcome for pro T-ALL in adult patients.

Adolescent↗
PubMed1992

CD45RA expression by CD4 T lymphocytes in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD).

Little is known about the role of tumor infiltrating T lymphocytes (TIL-T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved. In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 +/- 15.0% in B-cell NHL, and 37.4 +/- 18.6% in HD) than in reactive hyperplasia (54.7 +/- 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment. A further heterogeneity in the relative proportion of naive and memory TIL-T was also observed within lymphoma (range: 11 to 68% in B-cell NHL, 5 to 69% in HD). In B-cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P less than .0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 +/- 7.4%) than class 3 NHL, which are more aggressive (40.1 +/- 16.1%). Among the monoclonal antibodies (mAb) defining the B-cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (P = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL-T, activated CD3 DR TIL-T, or CD4 subset.

Adult↗
PubMed1992

Rearrangements of the upstream regulatory region of human papillomavirus type 6 can be found in both Buschke-Löwenstein tumours and in condylomata acuminata.

Clinically malignant Buschke-Löwenstein tumours and benign condylomata acuminata are caused by human papillomaviruses (HPVs), predominantly HPV-6 and -11. In some cases, the HPV-6 genomes found in Buschke-Löwenstein tumours and in verrucous carcinomas differ from HPV-6b isolated from a benign genital wart, by rearrangements of the upstream regulatory region (URR). To evaluate the frequency and role of mutations of the URR of HPV-6 we analysed 42 condylomata acuminata and four Buschke-Löwenstein tumours by the polymerase chain reaction and restriction enzyme cleavage. Using only four different restriction enzymes we could demonstrate four distinct restriction patterns, indicating that naturally occurring HPV-6 isolates display a high degree of DNA polymorphism within the URR. One Buschke-Löwenstein tumour and two condylomata acuminata yielded rearranged URRs with DNA duplications. All three lesions harboured multiple HPV-6 variants, suggesting that cellular or environmental factors facilitate the development of rearrangements. Therefore, rearrangements of the URR may represent only secondary events in condylomata acuminata and Buschke-Löwenstein tumours which do not necessarily confer a higher malignant potential to the infected cell.

Base Sequence↗
PubMed1992

Human papillomavirus (HPV) types specific of epidermodysplasia verruciformis detected in warts induced by HPV3 or HPV3-related types in immunosuppressed patients.

Epidermodysplasia verruciformis (EV) is characterized by an abnormal genetic predisposition to infection with specific types of human papillomavirus (HPV). Specific defects of the cell-mediated immunity and/or of the control of HPV infection in keratinocytes are assumed to be involved in the development of the disease. As a model to test this hypothesis, we have studied the prevalence of EV-specific HPV in skin warts of 56 immunosuppressed patients. All main types of cutaneous HPV (HPV1, 2, 3, 4, 10, and 28) responsible for skin warts in the general population were detected by blot hybridization. EV-specific HPV (HPV5, 20, and 23) were detected in three patients. Four additional patients were found infected with HPV49, first characterized in the course of this study, and found to be related to EV HPV. A most important finding was that HPV5, 20, 23, and 49 were always codetected with HPV3 or the related types HPV10 and 28. None of the specimens showed the typical clinical morphology of EV lesions. In none of these specimens was the specific cytopathic effect of EV recognized; instead that of HPV3 and related types was seen. No evidence for productive EV HPV DNA replication was obtained for the three specimens that could be further analyzed by in situ hybridization. Our data suggest that HPV3 infection favors infection with EV HPV in immunosuppressed patients but that the full expression of EV HPV is usually restricted as in the general population.

Adult↗
PubMed1991

Membrane cell permeabilization with saponin and multiparametric analysis by flow cytometry.

Saponin, a detergent like molecule, can permeabilize cell membranes without destroying them, and thus can be used for the detection of intracellular antigens on intact cells with a flow cytometer. First experiments were reported that demonstrated the detection of intracytoplasmic antigens such as intermediate filaments and CD3 in T acute lymphoblastic leukemia (ALL). Further experiments were also performed to prove that intranuclear structures were equally accessible: dyes such as propidium iodide (PI) and monoclonal antibodies (mAb) such as Ki67 could penetrate the nucleus and lead to the analysis of DNA content and to the discrimination between the different cell cycle phases (G0, G1, S, G2-M). This rapid and sensitive method retained sufficient integrity of cells being treated to enable differentiation of cell types on the basis of morphology. Furthermore, it did not alter membrane expression of most antigens. Therefore, it was of particular interest for multiparametric analysis, especially for simultaneous study of membrane and intracellular structures.

Aneuploidy↗
PubMed1991

Genetic heterogeneity among human papillomaviruses (HPV) associated with epidermodysplasia verruciformis: evidence for multiple allelic forms of HPV5 and HPV8 E6 genes.

In order to get some insight into modifications of human papillomavirus (HPV) genomes which could play a role in tumor progression in epidermodysplasia verruciformis (EV), we studied three EV patients infected by HPV5 and one by HPV8, with cancers containing mostly or only episomal viral genomes with a deletion. The mutants were compared with the full-length genomes present in the benign lesions of each patient. Deletions affected the L1 and/or L2 open reading frames (ORFs), and extended in the 5' end of the long control region in two cancers. The isolates studied showed a polymorphism of restriction endonuclease cleavage sites and variations in the nucleotide sequence of the E6 ORF and the regions flanking the deletions. However, except for one patient infected by two distinct HPV5 variants, no difference was observed in the nucleotide sequence of isolates cloned from the benign lesions and the cancer of the same patient. This may suggest that point mutations are not involved in tumor progression. Comparison of nucleotide sequence data revealed an unexpectedly high number of nucleotide substitutions among the four HPV5 variants and the HPV8 variant, as compared with HPV5 and HPV8 published sequences. Changes involved 49 of the 457 nucleotides of HPV5 E6 ORF and 14 of the 465 nucleotides of HPV8 E6 ORF. This corresponds to amino acid substitutions affecting 17 of the 157 amino acids of HPV5 E6 proteins and 7 of the 155 amino acids of HPV8 E6 proteins. Half of the substitutions represent nonconservative changes. The variants showing the highest degree of sequence variation were detected in additional EV patients by PCR. This points to the existence of a set of HPV5 and HPV8 stable variants, encoding for multiple allelic forms of the transforming E6 gene.

Alleles↗