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Biomedical subjects

F Richard

Publications and source records attributed to F Richard.

At least 145 records · Page 8Linked to original sources

[Several transcription factors participate in the functioning of the alpha-fetoprotein gene promoter].

The oncodevelopmentally regulated alpha-fetoprotein (AFP) gene offers a very good model system to better understand the molecular mechanisms which dictate the specificity of gene expression in liver and control its tight modulation in the course of development and carcinogenesis. Transcription factors of the CCAAT/enhance-binding protein (C/EBP), hepatocyte nuclear factor-1 (HNF-1), and nuclear factor-1 (NF-1) families can bind in vitro to the promoter of the rat AFP gene, which makes the expression of the AFP gene specific to the liver. We have evaluated the influence of some of these factors on the activity of the AFP promoter by transfection of HepG2 hepatoma cells with the appropriate expression vector plus a CAT plasmid under the control of the AFP promoter. A similar plasmid bearing the rat albumin promoter was used as a control. C/EBP alpha, and C/EBP beta acted as transactivators on the AFP promoter, while LIP, a truncated form of C/EBP beta, was a potent negative regulator of the promoter. Interestingly, HNF-1 beta was found to be more potent than HNF-1 alpha in activating the AFP promoter in the HepG2 cells. This effect was highly promoter and cell specific since it did not occur with the rat albumin promoter or in Chinese hamster ovary cells. HNF-1 beta, which is produced earlier than HNF-1 alpha during liver development, would thus have the greater influence on the AFP promoter in early development. Our results pointed to a key role that NF1 might play in the functioning of the AFP promoter. Indeed, overexpression of NF1 induced a specific decrease in the activity of the AFP promoter. Competition between NF1 and HNF-1 for binding to their overlapping binding sites on the AFP promoter would be critical for modulating its activity.

Animals↗

[Artificial urinary sphincter].

The artificial urinary sphincter is a totally implantable hydraulic prosthesis designed to restore continence without inducing dysuria. It is composed of 3 silicone elastomer elements: a periurethral or pericervical cuff, a pressure regulating reservoir balloon inserted in the retropubic space, and a pump situated in the scrotum or labia majora. The prosthesis is filled with a liquid containing a contrast agent. Pressure on the pump allows passage of liquid from the cuff towards the balloon and allows micturition. After 3 to 4 minutes, the liquid is automatically transferred from the balloon to the cuff to restore continence. The artificial sphincter is currently a very effective therapeutic solution in cases of severe urinary incontinence with 3 main indications: persistent incontinence after prostatic surgery, recurrent incontinence in women due to sphincter insufficiency, and certain forms of neurogenic incontinence. The Pitié-Salpêtrière Urology Department's experience currently consists of 200 implantations performed over the last 10 years. The overall success rate varies from 80 to 90% according to sex and the aetiology of incontinence, in patients in whom the sphincter remains in place. In fact, there is a risk of explantation due to erosion of the tissues by the cuff or infection, but this risk is less than 15%. The risk of prosthesis failure is about 20%, but after correction of the defective element, cure is achieved in almost every case. Analysis of the results in the first 120 patients with the two most frequent aetiologies and with at least three years' follow-up (range: 3 to 10 years) reveals: in a series of 75 men, treated for severe incontinence persisting more than one year after surgery for benign prostatic hyperplasia, the explantation rate was 15% and, in the patients in whom the sphincter remained in place, complete cure was obtained in 73% of cases without any incontinence, while 17% of patients suffered from minimal incontinence, not requiring protection, 7% had moderate incontinence requiring protection and 3% were considered to be failures. The revision rate for technical failure was 24%. In a series of 45 women with recurrent incontinence after surgery, due to sphincter insufficiency, the explanation rate was 13% and, in women in whom the sphincter remained in place, complete success was obtain in 78% of cases without any incontinence, while 17% suffered from minimal incontinence, usually not requiring protection, 5% require protection, with no failures and a revision rate for technical failure of 24%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Dose-effect relationship for in vivo and in vitro induction of dicentric aberrations in blood lymphocytes of children.

Chromosome aberrations induced in vivo were studied in nine children 5-12 years old treated with total-body high-energy photon irradiation (pulsed exposure from a LINAC) for different types of malignant diseases. Dose-effect relationships were obtained for each child by taking blood at different times during exposure. In vitro dose-effect relationships for chromosome aberrations in children and adults were obtained by exposing blood under the same conditions as the children. Exposure in vivo and in vitro yielded similar linear-quadratic dose-effect relationships for dicentric aberrations. The response in vitro was slightly greater than in vivo, but the difference was not very large. It is concluded that the dose-effect relationship for dicentric chromosome aberrations obtained in vitro for adults can be used for biological dosimetry in irradiated children. Some of the children displayed a high number of "rogue cells" before exposure; this may be due to the malignant disease as it was not found in the healthy controls.

Adolescent↗

[Use of the micronucleus test for biological dosimetry in cases of homogeneous or non-homogeneous exposure to ionizing radiations].

The dose effect relationship after homogeneous irradiation and the effect on the Poisson distribution of adding non-irradiated blood and thereby simulating non homogenous accidental exposure were studied for dicentric aberrations and micronuclei in lymphocytes exposed in vitro to 60Co gamma irradiation. The dose effect relationship for both parameters was of the linear quadratic type with the micronuclei responding slightly less to radiation than the dicentrics but a greater number of cells can easily be screened for micronuclei than for dicentrics. Except for one dose level in micronuclei, no deviations from the Poisson distribution were observed, after homogeneous tradition, but such a deviation was evident when non-irradiated blood was added to the irradiated one. With the help of the method of the "contaminated Poisson distribution" the proportion as well as the dose of the exposed blood could be approximately estimated. In order to test the suitability of the micronucleus test in vivo, both dicentrics and micronuclei were determined in patients treated for seminoma to an abdominal field. The data showed a consistent increase in both parameters without a significant difference between patients. The increase of both types of anomalies corresponded about to that expected from the size of the field exposed. The data from micronuclei appear, therefore, about as reliable for biological dosimetry as those from dicentrics for biological dosimetry after homogeneous and non-homogeneous exposure to ionizing radiations.

Adult↗

[Epidemiology of prostate cancer and its implications in public health].

Among potentially fatal cancers, prostatic cancer has the peculiarity of a considerable difference between a high prevalence of characteristic histological lesions and a low clinical prevalence (low prevalence of clinical manifestations?). Its second peculiarity is a prevalence that clearly increases with age. These two notions, no doubt partially linked to slow tumour growth, explain the present difficulties in defining a screening or a diagnostic strategy for this type of cancer. Aging of the population, with the "baby boomers" reaching ages that are affected by prostatic cancer, diagnostic methods that despite progress are still imperfect, and a probable real increase in the incidence of cancer underline the need for epidemiologic studies on prostatic cancer and its consequences.

Aged↗

Chromosome instability in lymphocytes from patients affected by or genetically predisposed to colorectal cancer.

To determine whether there are chromosomal clues to inherited forms of colorectal cancer, we studied chromosome instability in lymphocytes cultured from persons with sporadic colorectal cancer before treatment and from persons with a genetic predisposition to colorectal cancer due to adenomatous polyposis coli, Peutz-Jeghers syndrome, or juvenile polyposis. Spontaneous aberrations of chromosome number and structure were scored and compared to control studies by the same methods. Sex chromosome aneuploidy was found increased in patients. Autosomal aneuploidy was not increased. Chromosome breakage was elevated in young persons genetically predisposed to colorectal cancer compared to young patients with sporadic colorectal cancer. Chromosome rearrangements, other than those of chromosomes 7 and/or 14, rose with age, particularly in patients. Despite considerable interindividual variations, it would seem that increased chromosome breakage and rearrangement in addition to sex chromosome aneuploidy may be signs of chromosome instability in the predisposition to colorectal cancer.

Adenomatous Polyposis Coli↗

The frequency of micronuclei with X chromosome increases with age in human females.

The rate of micronuclei counted on lymphocyte cultures from five healthy female donors, 27-80 years old, increased with age. Using pXBR1 probe, specific for the alphoid DNA of the X chromosome, the presence of this chromosome was investigated by FISH (fluorescence in situ hybridization) in both micronuclei and metaphases. Both X aneuploidy and frequency of X chromosome per micronuclei increased with age. However, this overinvolvement of X chromosome was not sufficient to explain the overall increase of micronuclei with age, suggesting that autosomes are also involved. Thus, the higher increase of X than autosome aneuploidy in lymphocytes may result from both an excess of X chromosome losses and a better survival of cells with a monosomy X.

Adult↗

Tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in patients with renal cell carcinoma.

Patients with renal cell carcinoma (RCC) can exhibit fever, weight loss and increases in acute phase proteins. Interleukin (IL)-1, tumour necrosis factor (TNF) and IL-6 are considered major mediators of local and systemic inflammation. We measured plasma IL-1 beta, TNF-alpha (immunoradiometric assay) and IL-6 (ELISA) in 78 consecutive patients with untreated RCC and in 56 normal subjects. IL-6 plasma levels were higher in patients with RCC (mean 24.2 pg/ml, 11.1-37.3, 95% confidence interval) than in normal subjects (11.6 pg/ml, 10.1-13.1, n = 39, P < 0.01). The patients with fever or weight loss had higher blood levels of IL-6. IL-6 blood levels were also higher in patients with lymph node invasion and/or distant metastases (94.7 pg/ml, 39.0-150.4, n = 15) than in patients with undisseminated RCC (7.4, 4.1-10.7, n = 63, P < 0.0001). An abnormal IL-6 plasma value (> 40 pg/ml) had a positive predictive value of 91.0% for lymph node and/or metastatic spread of RCC. IL-6 was statistically correlated with C-reactive protein (nephelometric assay) blood values r' = 0.67, n = 78, P < 0.001). The TNF-alpha and IL-1 beta levels were not significantly different in patients with or without fever or weight loss. The plasma levels of the three cytokines were not correlated with the size of the primary tumour. An increased plasma value of IL-6 is a good marker for tumour dissemination in patients with untreated RCC.

Adult↗

Results of an epidemiological survey using a modified American Urological Association symptom index for benign prostatic hyperplasia in France.

The prevalence of urinary symptoms associated with benign prostatic hyperplasia was studied in a community-based, nationwide, representative sample of 2,011 French men 50 to 80 years old. Symptoms were assessed by the American Urological Association symptom index. After exclusion of patients with prostate cancer, 6.9% of the subjects reported having undergone prostate surgery. Among the surgery-free subjects, nocturia and repeat voiding within 2 hours were the most prevalent symptoms. Based on the American Urological Association symptom index, 18.8% of the men were considered free of urinary symptoms, and 67%, 13% and 1.2%, respectively, ranked between 1 and 7, 8 and 19, and 20 or more. The proportion of men scoring greater than 7 approximately doubled with each decade of age. Our estimation indicated that in 1992 approximately 1.14 million French men had moderate to severe urinary symptoms that were likely to be associated with benign prostatic hyperplasia. Previous studies had yielded higher prevalence estimates, probably due to differences in sampling design and diagnostic criteria.

Aged↗

Increased FISH efficiency using APC probes generated by direct incorporation of labeled nucleotides by PCR.

Probes of various sizes from the adenomatous polyposis coli gene (APC) were directly biotinylated by polymerase chain reaction (PCR) from genomic DNA. PCR labeling gave high efficiency in detection of fluorescence in situ hybridization (FISH) signals. Probes as small as 250 base pairs could be visualized through a fluorescence microscope without any image processing.

Adenomatous Polyposis Coli↗

Studies of neuroregulators in the brain stem of SIDS.

Some dysmaturity of neuroregulator neuronal systems may be responsible for brain stem disorders. These disorders may partly explain the mechanism of death in SIDS. The available data using microbiochemical assays, immunocytochemical techniques and autoradiographic methods seem to show anomalies of some monoaminergic and of some peptidergic systems, especially in the medulla oblongata. All these data need to be confirmed by further studies. It should be understood that one positive effect of such neuroanatomical study on SIDS is to gain 'normative' data on the human brain during development.

Brain Stem↗

Development of fast neutron therapy worldwide. Radiobiological, clinical and technical aspects.

Radiobiological data indicate that fast neutrons could bring a benefit in the treatment of some tumour types, and suggest mechanisms through which this benefit could be achieved. However, radiobiology also clearly indicates that there is a need for patient selection as well as for a high-physical selectivity. The main difficulty when interpreting the results of neutron therapy are the poor technical conditions in which the first treatments were applied. This explains why the value and the place of neutron therapy are not universally recognized, although more than 15,000 patients have been treated so far worldwide. There are, however, clinical indications of fast neutrons bringing a benefit for the following tumour sites: salivary glands, paranasal sinuses, soft tissue sarcomas, prostatic adenocarcinomas, palliative treatment of melanoma and rectum. These tumours represent about 10-15% of all patients currently referred to the radiation therapy departments.

Academies and Institutes↗

[Torsion of the spermatic cord. Current controversies].

The diagnosis of torsion of the spermatic pedicle is primarily clinical, despite the many studies concerning the value of complementary investigations. Currently available imaging modalities are limited either by their lack of sensitivity or by their lack of availability. The absence of well established evidence of direct impairment of contralateral testicular exocrine function is in favour of conservative treatment whenever the local conditions are suitable.

Humans↗

[Imaging of acute pyelonephritis].

Despite the advances achieved in imaging methods, the diagnosis of acute pyelonephritis rests on clinical and bacteriological date. Yet imaging is of considerable value to exclude a possible obstacle in the excretory canals which might be responsible for acute pyelonephritis. Ultrasonography associated with plain abdominal radiography without preparation or with intravenous urography is the choice method. In case of atypical forms, patients at risks or resistance to medical treatment, computerized tomography provides an information that is invaluable for the diagnosis as well as for the prognosis.

Acute Disease↗

Is it possible to verify directly a proton-treatment plan using positron emission tomography?

A PET camera is used to visualize the positron activity induced during protonbeam therapy in order to verify directly the proton-treatment plans. The positron emitters created are predominantly the 15O and 11C, whose total activity amounts to 12 MBq after an irradiation with 85 MeV protons, delivering 3 Gy in a volume of approximately 300 cm3. Although this method is a useful verification of patient set-up, care must be taken when deriving dose distributions from activity distributions. Correlation between both quantities is difficult, moreover at the last millimeters of their range, protons will no longer activate tissue. Due to the short half-lives the PET camera must be located close to the treatment facility.

Humans↗