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Biomedical subjects

M Favre

Publications and source records attributed to M Favre.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Characterization of human papillomavirus type 66 from an invasive carcinoma of the uterine cervix.

Human papillomavirus (HPV) DNA sequences coexisting with HPV16 and HPV45 were cloned from an invasive cervical carcinoma. The cloned HPV was shown to be a novel type, named HPV66, and is related to HPV56 (an HPV detected in cervical cancer). After screening 160 anogenital biopsies, four specimens exhibited histological features of intraepithelial neoplasia and contained HPV66 sequences. Of these, three were found to be associated with another HPV type.

Amino Acid Sequence↗
PubMed1990

Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA.

Human papilloma virus (HPV) DNA sequences (HPV types 16, 18, 33, 35 or uncharacterized) were detected by Southern blot hybridisation and polymerase chain reaction in 84% of 106 early-stage invasive carcinomas of the uterine cervix. Among HPV-positive patients, the risk of overall relapse did not differ with individual HPV types. Compared with HPV-positive patients, those with no detectable HPV DNA had a 2.6 times higher risk of overall relapse (p less than 0.05) and 4.5 times higher risk of distant metastases (p less than 0.01). The 24-month relapse-free survival rate in HPV-positive patients was significantly higher than that in HPV-negative patients (77% vs 40%), and the difference was similar (91% vs 56%) among those who were node-negative. These data indicate that HPV-negative cervical carcinomas may represent a biologically distinct subset of tumours that carry a poorer prognosis than do HPV-positive cancers.

Adenocarcinoma↗
PubMed1990

Two new human papillomavirus types (HPV54 and 55) characterized from genital tumours illustrate the plurality of genital HPVs.

The genomes of two new human papillomavirus (HPV) types, named HPV54 and HPV55, were cloned from penile lesions of 2 patients. HPV54 was isolated from a verrucous carcinoma (Buschke-Löwenstein tumour) together with full-length HPV6 genomes and HPV6 DNA molecules with a deletion of about 0.3 kb located in the non-coding region. HPV55 was isolated from a condyloma acuminatum. No cross-hybridization was observed between HPV54 DNA and the DNAs of the known cutaneous and genital HPVs by blot hybridization experiments performed under stringent conditions. In contrast, significant cross-hybridization was detected between HPV55 DNA and the DNA of HPV13, associated with benign oral lesions, and, to a lesser extent, with the DNAs of HPV6, 11, and 44, associated with benign genital proliferative lesions. The DNA sequence homology between HPV55 and HPV6, 11, and 13 was estimated at 12%, 12%, and 20%, respectively, by hybridization in liquid phase at saturation, followed by nuclease S1 analysis. The physical maps of HPV54 and 55 were aligned with the genetic maps of HPV16 and 11, respectively, by heteroduplex mapping and partial DNA sequencing. HPV54 is thus only weakly related to the known HPVs, while HPV55 represents an additional HPV6-related HPV type. HPV54 and HPV55 are uncommon genital HPV types since, in a survey of a large series of specimens of benign, pre-malignant or malignant anogenital and orolaryngeal tumours, HPV54 was not detected, and HPV55 was found in another case of condyloma acuminatum.

Adult↗
PubMed1990

Condylomata acuminata in children: frequent association with human papillomaviruses responsible for cutaneous warts.

To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation.

Adult↗
PubMed1990

Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.

To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.

Aged↗
PubMed1990

Comparison of outcome, clinical, laboratory, and immunological features in 164 children and adults with T-ALL. The Groupe d'Etude Immunologique des Leucémies.

T cell acute lymphoblastic leukemia (T-ALL) is a disease of poor prognosis, usually studied separately in adults or children. Controversial clinical or biological prognostic factors have been reported, and little information is available regarding the frequency and prognostic value of membrane markers identified on blast cells. We report an extensive investigation of the incidence and prognostic value of immunophenotypic, clinical, and laboratory data in T-ALL, performed as a multicenter study in 164 patients. CD7, CD5, and CD2 were the most frequently expressed T cell antigens, and CD2 and CD4 were more frequently observed in children than in adults. MHC class II, CD9, and CD10 were observed in 16, 22, and 21% of the patients, respectively. The male prevalence of T-ALL, and the more frequent presence of a tumoral syndrome in children were confirmed, but mediastinal enlargement and high leukocyte counts were observed in less than half the patients. A poor prognosis was associated with the expression of MHC class II in adults. The presence of a mediastinal mass appeared to be of good prognosis in adults, as well as a leukocyte count lower than 100 x 10(9)/l whatever the age of the patient.

Adolescent↗