Biomedical subjects

F Clavel

Publications and source records attributed to F Clavel.

At least 55 records · Page 3Linked to original sources

PubMed1994

Kinetic analysis of HIV-1 early replicative steps in a coculture system.

During an acute human immunodeficiency virus (HIV) infection in vitro, different forms of unintegrated viral DNA accumulate in target cells. They include linear full-length HIV DNA molecules, which are the precursors of the integrated provirus, and two types of circular molecules (with one or two LTRs), whose role and mode of formation are not fully understood. To evaluate the intracellular fate of HIV unintegrated DNA, and to follow the formation of the two types of circular DNA molecules, the nuclear transport of viral DNA, and its integration in host cell DNA, we have designed a "DNA chase" assay. This assay is based on cocultivation of persistently HIV-1-infected H9 cells with uninfected MT4, allowing rapid accumulation of viral DNA, which is then blocked by addition of AZT. In this highly efficient, synchronous, one-step cycle infection system, HIV linear DNA can be detected on Southern blots as early as 4 hr after the start of the coculture. Subsequently, viral DNA that had been synthesized before the addition of AZT could be "chased," establishing that almost all linear DNA molecules are rapidly transported to the nucleus, where they are either processed into the two types of circles or integrated. We could estimate that from the number of viral DNA molecules synthesized in 6 hr in this system, at least a third will become integrated and another third will circularize within 24 hr.

Biological Transport↗

PubMed1994

Fusion from without directed by human immunodeficiency virus particles.

Fusion from without is the process through which particles of some enveloped viruses can direct fusion of target cells in the absence of viral replication. We demonstrate here that human immunodeficiency virus (HIV) particles can efficiently promote fusion from without. Using HeLa-CD4 cells carrying a Tat-inducible lacZ gene, we observed syncytia as early as 6 h after exposure to HIV particles, before HIV gene expression could be detected. Efficient syncytium formation could be obtained when cells were treated with zidovudine, which prevented HIV replication and expression but not cell-cell fusion. Fusion was also observed when cells were exposed to particles of a replication-defective HIV integrase mutant. Fusion from without by HIV particles could be blocked by a monoclonal antibody specific for the V3 loop of the HIV-1 envelope glycoprotein and by soluble CD4. This mechanism of cytopathicity, which can involve cells that do not actively replicate HIV and can be directed by replication-defective particles, could participate in the pathogenicity of the CD4 cell depletion that characterizes HIV infection.

1-Deoxynojirimycin↗

PubMed1994

Familial risk of breast cancer in a French case-control study.

The relationship between a family history of cancer and the risk of breast cancer was investigated in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in families. This relationship increased linearly with both the number of the affected relatives and with the degree of kinship between the affected relative and the case. The highest risk was observed when a sister was affected by breast cancer. This could be explained by longer common environmental exposures between sisters than between mother and daughter. This could also be explained by a genetic factor segregating under a recessive model. The risk of breast cancer associated with colon, uterus, ovary, and prostate cancer in the family was not significantly different from one. However, the estimated odds ratios associated with a family history of colon cancer increased with the degree of kinship between the affected relative and the case in a similar manner to those of breast cancer. A relationship between the risk of breast cancer and a family history of colon cancer would support the existence of a common familial factor (be it genetic or not) for these cancers. Further genetic epidemiological studies might help to define the mode of inheritance of the same susceptibility to cancer at different sites.

Adult↗

PubMed1994

Familial risk of breast cancer and abortion.

We found that the risk of breast cancer associated with a family history of breast cancer increased with the number of abortions (induced as well as spontaneous) in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. For the women who had undergone at least two abortions, the risk associated with a family history did not seem to depend on the type of abortion. This finding suggests that the effect of a family history on the risk of breast cancer is modified by event(s) resulting from abortions. Further epidemiological studies should be conducted to verify the existence of this interaction.

Abortion, Induced↗

PubMed1993

Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.

In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.

Adolescent↗

PubMed1993

Reversion of a polymerase-defective integrated HIV-1 genome.

The 8E5 clonal cell line, derived from HIV-1-infected CEM cells, carries a single, reverse transcriptase (RT)-defective copy of an integrated HIV genome. The absence of RT production is a consequence of a frame shift in the pol gene, due to the addition of a single base at position 3241. We report here that 8E5 cells produce an infectious virus that can be serially passaged on CD4+ lymphoid cells. This virus (8E5R) is RT positive, but displays a slow replication profile, together with a reduced cytopathic effect. The nucleotide sequence of a segment of the pol region produced by PCR amplification of DNA from 8E5R-infected cells shows that the single nucleotide insertion characteristic of the 8E5 genome had been corrected. The same reversion event was also found to occur in most single-cell clones derived from the 8E5 cell line. Because this cell line is used in many laboratories, notably as a standard for PCR quantitation, and is generally considered as unable to produce infectious virus, our findings should prompt investigators to use particular care in the handling of these cells.

Base Sequence↗

PubMed1992

[New virological data: replication and persistence of the human immunodeficiency virus].

Human immunodeficiency virus behaves in vitro as an acutely replicating, cytopathic retrovirus. However, HIV infection in vivo is persistent and slowly progressive. Many virological properties of HIV could be involved in establishing the persistence of infection: the complex regulation of HIV replication, particularly of HIV gene expression; the requirement of cell activation for several steps of HIV replication; the role of HIV accessory genes; the great genetic variability of HIVs, allowing their adaptation to host responses in vivo.

CD4-Positive T-Lymphocytes↗

PubMed1992

A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication.

We recently reported that human immunodeficiency virus type 1 (HIV-1) unintegrated linear DNA displays a discontinuity in its plus strand, precisely defined by a second copy of the polypurine tract (PPT) located near the middle of the genome (P. Charneau and F. Clavel, J. Virol. 65:2415-2421, 1991). This central PPT appears to determine a second initiation site for retrovirus DNA plus-strand synthesis. We show here that mutations replacing purines by pyrimidines in the HIV-1 central PPT, which do not modify the overlapping amino acid sequence, are able to significantly slow down viral growth as they reduce plus-strand origin at the center of the genome. One of these mutations, introducing four pyrimidines, results in a 2-week delay in viral growth in CEM cells and abolishes plus-strand origin at the central PPT. The introduction in this mutant of a wild-type copy of the PPT at a different site creates a new plus-strand origin at that site. This new origin also determines the end of the upstream plus-strand segment, probably as a consequence of limited strand displacement-synthesis. Our findings further demonstrate the role of PPTs as initiation sites for the synthesis of the retroviral DNA plus strand and demonstrate the importance of a second such origin for efficient HIV replication in vitro.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Complementation of murine cells for human immunodeficiency virus envelope/CD4-mediated fusion in human/murine heterokaryons.

Murine cell lines expressing human CD4 are resistant to the fusogenic effect of the human immunodeficiency virus (HIV) envelope. Consequently, they cannot be infected by HIV or form syncytia with HIV envelope-expressing cells. Murine cells could either lack human-specific cofactors necessary for the CD4/envelope-mediated membrane fusion or express inhibitors of this process. To address this question, we have tested the ability of heterokaryons made from CD4-expressing murine cells and human cells to undergo HIV envelope-mediated fusion. We have devised a rapid and specific assay based on the induction of lacZ expression, in which membrane fusion events with HIV-infected cells can be detected by a simple histochemical technique. CD4-positive murine/human heterokaryons, but not murine/simian heterokaryons, were found able to fuse with HIV envelope-expressing cells. In these experiments, the fusion resistant phenotype of murine-CD4 cells could be complemented by human cellular factors.

3T3 Cells↗

PubMed1991

Association between breast cancer and family malignancies.

In a case-control study, the relationship between a family history of cancer of the breast, ovary, colon, uterus or prostate and the risk of breast cancer was investigated. The data consisted of family histories from 495 breast cancer cases and 785 controls aged 20-56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in the families of the subjects affected. This relationship increased linearly with both the degree of kinship of the affected relatives and with their number. The risk of breast cancer associated with other types of cancer in the family was not significantly different from unity.

Adult↗

PubMed1991

Oral contraceptives and breast cancer: a French case-control study.

The relationship between the risk of breast cancer and oral contraceptive use was investigated in a case-control study conducted in France between 1983 and 1987 in five public hospitals. Some 464 cases aged 25 to 56 years and 542 matched controls were interviewed about their history of the use of oral contraceptives (OC). Results are given for the entire population and for the subgroup of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever user, was 1.5 (p less than 0.01) in the whole group as well as in the premenopausal subgroup (p less than 0.02). However, there was no evidence that the effect varied appreciably according to duration of use, age at first use, use before first full-term pregnancy (FFTP) and time since first or last use. The risk was not altered for any particular brand of OC. We conclude that, because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for part of the excess in risk observed among OC ever users.

Adenocarcinoma↗

PubMed1991

A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract.

The structure of unintegrated human immunodeficiency virus type 1 (HIV-1) DNA from acutely infected human lymphoid cells was analyzed by nuclease S1 cleavage. We observed a unique, discrete single-stranded gap in unintegrated linear DNA molecules, located near the center of the genome. Oligonucleotide primer extension experiments determined that the downstream limit of this gap coincides with the last nucleotide of a central copy of the polypurine tract found in all sequenced lentivirus genomes. Other retroviruses have only one copy of the polypurine tract at the 5' boundary of the 3' long terminal repeat, which has been shown to determine initiation of retroviral DNA plus-strand synthesis. We conclude from our observations that the central repeat of the polypurine tract can create an additional site for plus-strand synthesis initiation in lentiviruses. The central single-stranded gap was not found in circular DNA molecules, the vast majority of them carrying only one long terminal repeat. This finding suggests that the generation of such circular molecules is associated with early DNA ligation events.

Base Sequence↗

PubMed1991

Occupational exposure and cancer of the pancreas: a review.

Many hypotheses have been proposed about the aetiology of cancer of the pancreas, especially concerning the effects of tobacco, coffee, alcohol, diet, and pancreatic pathology. Results of numerous epidemiological studies are, however, inconsistent. Chemical carcinogens have been implicated as possible risk factors. Animal studies have been carried out to determine the role of these chemical factors but, except for nitrosamines and their derivatives (components of tobacco), chemicals have not been proved carcinogenic for the pancreas. Many studies have also been conducted among occupational groups. Several of them showed an excess risk of cancer of the pancreas, especially in the chemical and petroleum industries. The lack of accuracy about the nature of products used, however, does not permit a definitive conclusion as to their carcinogenic role. This paper is a review of publications about occupational exposures and cancer of the pancreas.

Adult↗

PubMed1990

Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1.

The retroviral genome consists of two identical RNA molecules joined at their 5' ends by the Dimer Linkage Structure (DLS). To study the mechanism of dimerization and the DLS of HIV-1 RNA, large amounts of bona fide HIV-1 RNA and of mutants have been synthesized in vitro. We report that HIV-1 RNA forms dimeric molecules and that viral nucleocapsid (NC) protein NCp15 greatly activates dimerization. Deletion mutagenesis in the RNA 5' 1333 nucleotides indicated that a small domain of 100 nucleotides, located between positions 311 to 415 from the 5' end, is necessary and sufficient to promote HIV-1 RNA dimerization. This dimerization domain encompasses an encapsidation element located between the 5' splice donor site and initiator AUG of gag and shows little sequence variations in different strains of HIV-1. Furthermore, cross-linking analysis of the interactions between NC and HIV-1 RNA (311 to 415) locates a major contact site in the encapsidation element of HIV-1 RNA. The genomic RNA dimer is tightly associated with nucleocapsid protein molecules in avian and murine retroviruses, and this ribonucleoprotein structure is believed to be the template for reverse transcription. Genomic RNA-protein interactions have been analyzed in human immunodeficiency virus (HIV) virions and results showed that NC protein molecules are tightly bound to the genomic RNA dimer. Since retroviral RNA dimerization and packaging appear to be under the control of the same cis element, the encapsidation sequences, and trans-acting factor, the NC protein, they are probably related events in the course of virion assembly.

Base Sequence↗

PubMed1990

Alcohol, beer and cancer of the pancreas.

The relationship between total alcohol consumption and intake of beer, wine and spirits and the risk of cancer of the pancreas was re-assessed in a pooled analysis of 3 case-control studies of pancreatic cancer from Italy, France and Switzerland, providing a total data-set of 494 cases and 1,704 controls. Logistic regression was used to obtain relative risks adjusted for study, age, sex, smoking and socio-economic status. Relative to non-drinkers, the risk estimates for subsequent levels of alcohol consumption were close to unity, and there was no evidence of a trend in risk with dose: the point estimate for more than 8 drinks per day was 0.8 (95% Confidence Interval, CI = 0.5-1.3). Likewise, no consistent association was observed for consumption of wine, beer or spirits: the relative risks for the highest consumption levels were 1.0 for wine, 0.9 for beer and 0.9 for spirits. No significant interaction was observed with study centre, sex or smoking habits. Given the large size of the data-set, of the consistency and the replication of findings across the 3 different studies, and of the elevated alcohol consumption of these populations, the present analysis gives reassuring evidence on the alcohol and pancreatic cancer issue in relation to total consumption of alcohol, of beer and of other alcoholic beverages.

Adult↗

PubMed1990

A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology.

A deletion of 30 bases was created in the noncoding region of the human immunodeficiency virus type 1 genome that extends between the 5' splice donor and the start of the gag gene. Viral particles produced after transfection of this mutant provirus had a normal protein pattern but a reduced RNA content. The infectivity of the mutant virus was also markedly reduced but not completely abolished. Electron-microscopic examination of the mutant virions revealed major abnormalities of the nucleoid structure, mostly related to the dense material characteristic of mature particles, suggesting that the presence of RNA is essential to the normal structure of the nucleoid.

Base Sequence↗

PubMed1990

Occupational risk factors for cancer of the pancreas: a case-control study.

The role of the occupational environment in the occurrence of cancer of the pancreas was analysed in a case-control study of 171 cases of pancreatic cancer and 317 controls matched for age at interview, sex, hospital, and interviewer. The study was conducted in France between 1982 and 1985 and covered 15 important industries and various other occupations. The results are given for the whole population, a subgroup of manual workers (46 cases and 108 controls), and a subgroup of French nationals (114 cases and 253 controls). After adjustment for cigarette smoking, and coffee and alcohol consumption, workers in the food industry (OR = 1.86) and the leather industry (OR = 1.63) showed higher risks than other industries. In the sub-group of French nationals only the risk associated with the textile industry was significantly higher than unity (OR = 2.30). No significant increase in risk was associated with work in any of the other branches studied; printing showed a moderate increase in risk (OR = 1.54). The subgroup of manual workers showed an increase in risk for cancer of the pancreas among those working in the building materials and building trades classification (OR = 2.16) and transportation (OR = 1.57).

Case-Control Studies↗

PubMed1990

[A study of various smoking cessation programs based on close to 1000 volunteers recruited from the general population: 1-month results].

The harmful effect of tobacco on health is well known. To help smokers to stop smoking, a study was designed in 1987 to assess the efficacy of two treatments and the advantage of combining them. The treatments, nicotine chewing gum and acupuncture, were randomly allocated. The 996 subjects required are now included. The characteristics of the participants, the number of nicotine gums used as well as the need for a cigarette are described. Cessation rates in the four groups, one month after the beginning of the treatment, differed significantly (p less than 5%). The efficacy of acupuncture was not shown (abstinence rates of 22 and 23% for the active and placebo groups respectively), whereas the efficacy of nicotine gum was (26 and 19% for the active and placebo groups respectively). The interest of the association of the two treatments was not observed.

Acupuncture Therapy↗