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Biomedical subjects

G Fournier

Publications and source records attributed to G Fournier.

At least 91 records · Page 5Linked to original sources

Glycosylated nature of testosterone 5 alpha-reductase 2 purified from human prostate.

5 alpha-reductase 2 from human prostate solubilized into an active and stable form using a non-ionic detergent octyl glucoside was successfully purified using a four-step chromatographic procedure. The enzyme was obtained as an apparently homogeneous protein exhibiting an apparent molecular weight of 42 kDa upon SDS-PAGE. Con A, DBA, UEA-I, and RCA60 lectins recognized this protein. After treatment with O-glycosidase and neuraminidase, a protein of an apparent molecular weight about 30 kDa appeared. On the other hand, N-glycosidase treatment of this enzyme had no effect. These results indicate that the human prostate testosterone 5 alpha-reductase 2 is an O-glycosylated sialoglycoprotein with a peptide moiety of about 30 kDa; the oligosaccharide side chains contain mannose, N-acetyl galactosamine, fucose, galactose and sialic acids.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Inhibition of tumorigenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid.

Prostate-specific antigen (PSA) is a member of the kallikrein family and has been an important biological marker for prostate cancer. The mechanisms regulating PSA expression in prostatic cancer cells are unclear. The present study was designed to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the tumorigenic potential of the human prostate cancer cell line LNCaP. The growth regulation of LNCaP cells was examined by DNA synthesis and doubling time. The tumorigenic potential of prostate cancer cells was analyzed by soft agar colony-forming assay, in vitro invasion assay, type IV collagenase assay and binding to extracellular matrix assay. The nuclear receptors for retinoic acid (RAR alpha, -beta, -gamma and RXR alpha, -beta, -gamma) as well as PSA mRNA were determined by Northern blot using specific oligonucleotide probes. Our results suggest that 13-cis-RA significantly inhibits PSA secretion and expression both at the mRNA and protein levels compared with untreated cells. Electron microscopic studies suggest that after 13-cis-RA treatment, cells become more differentiated as they contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell growth and tumorigenic potential after 13-cis-RA treatment was significantly decreased compared with controls. Nude mice tumorigenicity studies showed that 13-cis-RA-treated cells produced significantly smaller tumors compared with untreated cell tumors. There was also a significant increase in the expression of RXRa mRNA after 13-cis-RA treatment compared with untreated cells.

Animals↗

[Management of advanced prostate cancer].

Prostatic adenocarcinoma is still often detected at an advanced stage, despite efforts for earlier diagnosis. Treatment depends especially on the stage of the disease at the time of diagnosis, on potential development which varies among types of tumours, on the presence of symptoms related to local-regional or general dissemination, and on age, which may be advanced in these patients. In stage C cancers with limited extraprostatic dissemination, the use of radical prostatectomy is debated. It may be indicated in some selected young patients in association with hormonal treatment. In other cases, androgen control alone (early, or only after appearance of symptoms) or pelvic radiation therapy can be used. In the presence of metastases, hormonal control is the best means of slowing disease progression. It is always indicated when the disease is symptomatic. The various means of hormonal treatment (surgical castration, LH-RH agonists, anti-androgens) should be considered with regard to the status of the patient, the manifestations of cancer and potential side effects of treatment. Surgery and/or radiation therapy is indicated for symptomatic relief in treatment of local dissemination (extension to the urinary tract, etc.) or bone metastases. In case of hormonal treatment failure, no other treatment is really effective, and survival is short. Symptomatic treatments are then used to increase quality of life.

Adenocarcinoma↗

Genetic alterations in localized prostate cancer: identification of a common region of deletion on chromosome arm 18q.

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.

Alleles↗

The response to exercise with constant energy intake in identical twins.

Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 +/- 9.8 MJ (Mean +/- SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p < 0.001) and it was entirely accounted for by the loss of fat mass (p < 0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p < 0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomograply (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm2 (SEM = 5) to 52 cm2 (SEM = 6) (p < 0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p < or = 0.05). Intrapair resemblance was observed for the changes in body weight (p < 0.05), fat mass (P < 0.01), percent fat (p < 0.01), body energy content (p < 0.01), sum of 10 skinfolds (p < 0.01), abdominal visceral fat (p < 0.01), fasting plasma triglycerides (p < 0.05) and cholesterol (p < 0.05), maximal oxygen uptake (p < 0.05), and respiratory exchange ratio during submaximal work (p < 0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during submaximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.

Adipose Tissue↗

Purification of testosterone 5 alpha-reductase from human prostate by a four-step chromatographic procedure.

Nuclear membrane bound testosterone 5 alpha-reductase solubilized in active form from human prostatic tissue by 0.5% n-octyl beta-D-glucopyranoside was purified by a four-step chromatographic procedure including DEAE-Trisacryl ion exchange, hydroxylapatite adsorption, testosterone-Sepharose affinity and Sepharose 4B gel filtration. A purification of approximately 30-fold was achieved judging from the increase in the specific enzymatic activity. We have purified the acidic pH-optimum 5 alpha-reductase type 2 isoenzyme. The apparent molecular weight of the purified enzyme was estimated as 42,000 by SDS-PAGE. At the same time we isolated a 38 kDa protein characterized by a real affinity for testosterone and by a possible association to the 5 alpha-reductase enzyme.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Transurethral evaporation of prostate (TUEP) with Nd:YAG laser using a contact free beam technique: results in 61 patients with benign prostatic hyperplasia.

OBJECTIVE: This prospective study was undertaken to evaluate the safety and efficacy of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser for treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 61 patients at a mean age of 71.6 years with symptomatic bladder outlet obstruction due to BPH underwent transurethral evaporation of prostate (TUEP) using Nd:YAG laser. Twelve of the patients were experiencing acute retention. Pre- and postoperative evaluation consisted of American Urological Association (AUA) symptom questionnaire and a sexual function questionnaire, uroflowmetry, postvoid residual urine, electrolytes, blood urea nitrogen, creatinine, hematocrit, and prostate volume estimation by transrectal ultrasound. TUEP was achieved by employing a side-firing Nd:YAG laser fiber with a durable quartz reflector and high-power density (Ultraline, Heraeus LaserSonics, Milpitas, CA) that was used in a contact mode. RESULTS: All patients have been evaluated for three months, 26 for six months, and 7 for twelve months. Mean prostatic size was 41.1 g. The mean improvement in symptom scores at one, three, six, and twelve months was 69.8 percent, 70.9 percent, 76.0 percent, and 70.9 percent, respectively (P = < 0.0001). The mean increase in maximum uroflow at one, three, six, and twelve months was 63.4 percent, 66.7 percent, 41.94 percent, and 164.52 percent, respectively (P = < 0.0001). There was no instance of significant fluid absorption or bleeding. The duration of postoperative catheterization was two days in 43 patients, three to seven days in 16 patients, and two to three weeks in 2 patients. There were no deaths. All patients evaluated by TRUS at six months had open channeling defects. Videocystoscopy performed in 16 patients at two to three months postoperatively revealed tissue slough. At repeat cystoscopy in these patients at six months, the prostatic fossa was completely healed with no evidence of tissue slough. CONCLUSIONS: It is concluded that the technique of TUEP using Nd:YAG laser is safe and, in preliminary results, appears apparently effective in the management of BPH.

Aged↗

Utility of preoperative serum prostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer.

OBJECTIVES: To determine the accuracy of the preoperative serum concentration of prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy specimens in predicting the presence of disease in the pelvic lymph nodes in patients with prostate cancer. METHODS: The medical records of all patients treated for prostate cancer at eight medical centers from January 1988 to June 1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer for whom all relevant data were available who had undergone pelvic lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The rate of false-negative predictions of metastases based on combined preoperative biopsy Gleason score and serum PSA concentration was analyzed. A multivariate logistic regression analysis was performed to assess the value of preoperative serum PSA and biopsy Gleason scores individually and in combination in predicting pelvic lymph node metastases. RESULTS: The false-negative rate of metastases was 0% for preoperative PSA concentrations < or = 6 ng/mL and biopsy Gleason scores < or = 5 (n = 142) and 1.0% for PSA concentrations < or = 10 ng/mL and Gleason scores < or = 6 (n = 388). The 95% upper confidence limit for the rate of false negativity at this PSA cut-off level was 2.0%. A combination of preoperative serum PSA levels and biopsy Gleason scores provided the best prediction for the false-negative rates. CONCLUSIONS: For patients with newly diagnosed prostate cancer who have biopsy Gleason scores < or = 6 and preoperative PSA concentrations < or = 10 ng/mL (42% of our series), a staging pelvic lymphadenectomy appears to be unnecessary. The substantial cost associated with both cross-sectional imaging and staging lymphadenectomy may therefore be avoidable in this group of patients.

Biopsy↗

[Mid-term and long-term outcome in Leydig cell estrogen tumors].

A study has been realized in six patients with estrogen secreting Leydig cell tumors from 18 to 120 months after hemicastration. Testicular contralateral volume is normalized, gynecomastia can be completely reduced, sex steroids are normalized while gonadotropins can be temporary increased. Spermogram which is abnormal can be normalized. These results confirm the heterogeneity of these tumors.

Adult↗

[Percutaneous drainage nephrostomy in patients over 70 years of age. Apropos of 98 nephrostomies in 74 patients].

From 1985 to 1992, 98 ultrasound-guided percutaneous drainage nephrostomies were performed in 74 patients with a mean age of 77 years (range: 70-88 years). The diversion was indicated because of upper urinary tract obstruction (87% of cases), urinary fistula (4%) or secondary displacement of the first PCN (9%). The initial disease was benign in 29 patients (42.5%, including 48% of renal and ureteric stones), malignant in 39 cases (53%, including 79% of pelvic cancers) and not specified in 6 cases (4.5%). PCN was performed successfully in 93% of patients and allowed improvement in renal failure and/or treatment of the initial infectious syndrome in the majority of cases. The following complications were observed: secondary displacement of the drain (13 cases), infection (3 cases), renal subcapsular haematoma (1 case). The outcome of the patients was directly related to the initial disease: 28 of the 29 patients diverted for a benign disease were still alive and the PCN drain was able to be removed in 96% of cases after curative treatment; 95% of the patients diverted for cancer had died within 13 months after PCN. Patients with previously untreated prostatic cancer had the best prognosis, as androgen suppression allowed removal of the PCN without any additional procedure, in some cases. Drainage of the upper urinary tract by percutaneous nephrostomy under local anaesthesia has a limited morbidity and a low failure rate and therefore appears to be a technique of choice, particularly in elderly patients.

Aged↗

[A retrocaval ureter associated with contralateral pelvic renal ectopia.: use of a 3-dimensional scanner. Apropos of a case and review of the literature].

Retrocaval ureter is a rare malformation occasionally associated with other urological or nonurological abnormalities. We report an exceptional case of retrocaval ureter associated with contralateral pelvic ectopic kidney in a 22 year old man. The anomalies associated with the retrocaval ureter and the embryological mechanisms are described. Abdominal computed tomography with 3D reconstruction provided a new perspective of this malformation, but its clinical value remains unclear.

Adult↗

Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface.

p53 antibodies have been found in sera of patients with breast and lung carcinomas and in children with B-lymphomas. We report here the presence of p53 antibodies in sera of patients with 11 different types of cancer. The frequency of seropositives for p53 varied among the different types of cancer, but a correlation with the frequency of p53 gene alteration was established. Using a powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the immune response of patients with p53 antibodies was restricted to a small subset of peptides localized in the amino and carboxy termini of p53, whatever the type of cancer. Given the similarities of the patterns of immune responses in patients with p53 antibodies and animals hyperimmunized with human p53, we propose that the p53 humoral response is the result of a self-immunization process which is itself the consequence of p53 protein accumulation in tumor cells.

Amino Acid Sequence↗

The value of prostate specific antigen and transrectal ultrasound guided biopsy in detecting prostatic fossa recurrences following radical prostatectomy.

The combination of prostate specific antigen (PSA) and transrectal ultrasonography was used to detect recurrent cancer in the prostatic fossa after radical prostatectomy. A total of 43 patients with persistently elevated PSA levels and negative bone scintigraphy following radical prostatectomy underwent digital rectal examination and transrectal ultrasonography. Ultrasound findings were considered suspicious if the scan showed any unusual hypoechoic tissue adjacent to the bladder neck, retro-trigone or peri-anastomotic site. Of 22 patients (51%) with biopsy proved cancer 21 (95%) had positive transrectal ultrasonography, while digital rectal examination was able to detect cancer in only 10 (45%). Among transrectal ultrasonography detected recurrences 15 (68%) were detected at the initial biopsy and 7 (32%) at repeat biopsies. Our study shows that the combination of PSA and transrectal ultrasonography provides a more effective method than digital rectal examination and PSA to detect biopsy proved cancer following radical prostatectomy.

Adenocarcinoma↗